Estudio del potencial inhibitorio de las xantonas provenientes de Garcinia mangostana (Clusiaceae) sobre tres enzimas digestivas relacionadas con obesidad y diabetes tipo 2 en búsqueda de moléculas con acción multidiana

ilustraciones, fotografías, gráficas, tablas

Autores:
Cardozo Muñoz, Juan Camilo
Tipo de recurso:
Fecha de publicación:
2021
Institución:
Universidad Nacional de Colombia
Repositorio:
Universidad Nacional de Colombia
Idioma:
spa
OAI Identifier:
oai:repositorio.unal.edu.co:unal/79963
Acceso en línea:
https://repositorio.unal.edu.co/handle/unal/79963
https://repositorio.unal.edu.co/
Palabra clave:
540 - Química y ciencias afines
Diabetes Mellitus Tipo 2
Diabetes Mellitus, Type 2
Obesidad
Obesity
Lipasa pancreática
α-amilasa
α-glucosidasa
Xantonas
G. mangostana.
Pancreatic lipase
α-amylase
α-glucosidase
Garcinia mangostana.
Rights
openAccess
License
Atribución-NoComercial-SinDerivadas 4.0 Internacional
id UNACIONAL2_bca080533fc259c16bd718bd77c3a152
oai_identifier_str oai:repositorio.unal.edu.co:unal/79963
network_acronym_str UNACIONAL2
network_name_str Universidad Nacional de Colombia
repository_id_str
dc.title.none.fl_str_mv Estudio del potencial inhibitorio de las xantonas provenientes de Garcinia mangostana (Clusiaceae) sobre tres enzimas digestivas relacionadas con obesidad y diabetes tipo 2 en búsqueda de moléculas con acción multidiana
dc.title.translated.eng.fl_str_mv Study of the inhibitory potential of xanthones from Garcinia mangostana (Clusiaceae) on three digestive enzymes related to obesity and type 2 diabetes in search of molecules with multitarget action
title Estudio del potencial inhibitorio de las xantonas provenientes de Garcinia mangostana (Clusiaceae) sobre tres enzimas digestivas relacionadas con obesidad y diabetes tipo 2 en búsqueda de moléculas con acción multidiana
spellingShingle Estudio del potencial inhibitorio de las xantonas provenientes de Garcinia mangostana (Clusiaceae) sobre tres enzimas digestivas relacionadas con obesidad y diabetes tipo 2 en búsqueda de moléculas con acción multidiana
540 - Química y ciencias afines
Diabetes Mellitus Tipo 2
Diabetes Mellitus, Type 2
Obesidad
Obesity
Lipasa pancreática
α-amilasa
α-glucosidasa
Xantonas
G. mangostana.
Pancreatic lipase
α-amylase
α-glucosidase
Garcinia mangostana.
title_short Estudio del potencial inhibitorio de las xantonas provenientes de Garcinia mangostana (Clusiaceae) sobre tres enzimas digestivas relacionadas con obesidad y diabetes tipo 2 en búsqueda de moléculas con acción multidiana
title_full Estudio del potencial inhibitorio de las xantonas provenientes de Garcinia mangostana (Clusiaceae) sobre tres enzimas digestivas relacionadas con obesidad y diabetes tipo 2 en búsqueda de moléculas con acción multidiana
title_fullStr Estudio del potencial inhibitorio de las xantonas provenientes de Garcinia mangostana (Clusiaceae) sobre tres enzimas digestivas relacionadas con obesidad y diabetes tipo 2 en búsqueda de moléculas con acción multidiana
title_full_unstemmed Estudio del potencial inhibitorio de las xantonas provenientes de Garcinia mangostana (Clusiaceae) sobre tres enzimas digestivas relacionadas con obesidad y diabetes tipo 2 en búsqueda de moléculas con acción multidiana
title_sort Estudio del potencial inhibitorio de las xantonas provenientes de Garcinia mangostana (Clusiaceae) sobre tres enzimas digestivas relacionadas con obesidad y diabetes tipo 2 en búsqueda de moléculas con acción multidiana
dc.creator.fl_str_mv Cardozo Muñoz, Juan Camilo
dc.contributor.advisor.none.fl_str_mv Patiño Ladino, Oscar Javier
Lopez Vallejo, Fabian Harvey
dc.contributor.author.none.fl_str_mv Cardozo Muñoz, Juan Camilo
dc.contributor.researchgroup.spa.fl_str_mv Productos Naturales Vegetales Bioactivos y Quimica EcoIogica
dc.subject.ddc.spa.fl_str_mv 540 - Química y ciencias afines
topic 540 - Química y ciencias afines
Diabetes Mellitus Tipo 2
Diabetes Mellitus, Type 2
Obesidad
Obesity
Lipasa pancreática
α-amilasa
α-glucosidasa
Xantonas
G. mangostana.
Pancreatic lipase
α-amylase
α-glucosidase
Garcinia mangostana.
dc.subject.decs.none.fl_str_mv Diabetes Mellitus Tipo 2
Diabetes Mellitus, Type 2
Obesidad
Obesity
dc.subject.proposal.spa.fl_str_mv Lipasa pancreática
α-amilasa
α-glucosidasa
Xantonas
G. mangostana.
dc.subject.proposal.eng.fl_str_mv Pancreatic lipase
α-amylase
α-glucosidase
Garcinia mangostana.
description ilustraciones, fotografías, gráficas, tablas
publishDate 2021
dc.date.accessioned.none.fl_str_mv 2021-08-18T15:44:10Z
dc.date.available.none.fl_str_mv 2021-08-18T15:44:10Z
dc.date.issued.none.fl_str_mv 2021-08-17
dc.type.spa.fl_str_mv Trabajo de grado - Maestría
dc.type.driver.spa.fl_str_mv info:eu-repo/semantics/masterThesis
dc.type.version.spa.fl_str_mv info:eu-repo/semantics/acceptedVersion
dc.type.content.spa.fl_str_mv Text
dc.type.redcol.spa.fl_str_mv http://purl.org/redcol/resource_type/TM
status_str acceptedVersion
dc.identifier.uri.none.fl_str_mv https://repositorio.unal.edu.co/handle/unal/79963
dc.identifier.instname.spa.fl_str_mv Universidad Nacional de Colombia
dc.identifier.reponame.spa.fl_str_mv Repositorio Institucional Universidad Nacional de Colombia
dc.identifier.repourl.spa.fl_str_mv https://repositorio.unal.edu.co/
url https://repositorio.unal.edu.co/handle/unal/79963
https://repositorio.unal.edu.co/
identifier_str_mv Universidad Nacional de Colombia
Repositorio Institucional Universidad Nacional de Colombia
dc.language.iso.spa.fl_str_mv spa
language spa
dc.relation.references.spa.fl_str_mv Abarca-Gómez, L., Z. A. Abdeen, Z. A. Hamid, N. M. Abu-Rmeileh, B. Acosta-Cazares, C. Acuin, and C. Agyemang. 2017. “Worldwide Trends in Body-Mass Index, Underweight, Overweight, and Obesity from 1975 to 2016: A Pooled Analysis of 2416 Population-Based Measurement Studies in 128·9 Million Children, Adolescents, and Adults.” The Lancet 390(10113):2627–42.
Adnyana, I., A. Abuzaid, E. Iskandar, and N. Kurniati. 2016. “Pancreatic Lipase and α-Amylase Inhibitory Potential of Mangosteen ( Garcinia Mangostana Linn.) Pericarp Extract.” International Journal of Medical Research & Health Sciences 5(1):23.
Aguilar S., Carlos A., and Pablo. Aschner. 2019. “Guías ALAD Sobre El Diagnóstico, Control y Tratamiento de La Diabetes Mellitus Tipo 2 Con Medicina Basada En Evidencia Edición 2019.” Revista de La Asociación Latinoamericana de Diabetes.
Ah-Reum, Han, Jeong-Ah Kim, Daniel D. Lantvit, Leonarduz B. Kardonom, Soerdanoso Rsiwan, Heebyung Chai, Esperanza J. Carchate de blanco, Norman R. Farnsworth, Steven M. Swanson, and A. Douglas Kinghorn. 2009. “Cytotoxic Xanthone Constituents of the Stem Bark of Garcinia Mangostana (Mangosteen).” Journal of Natural Products 72(11):1–7.
Al-Goblan, Abdullah S., Mohammed A. Al-Alfi, and Muhammad Z. Khan. 2014. “Mechanism Linking Diabetes Mellitus and Obesity.” Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 7:587–91.
Alqahtani, Ali S., Syed Hidayathulla, Md Tabish Rehman, Ali A. Elgamal, Shaza Al-Massarani, Valentina Razmovski-Naumovski, Mohammed S. Alqahtani, Rabab A. El Dib, and Mohamed F. Alajmi. 2020. “Alpha-Amylase and Alpha-Glucosidase Enzyme Inhibition and Antioxidant Potential of 3-Oxolupenal and Katononic Acid Isolated from Nuxia Oppositifolia.” Biomolecules 10(1).
Aravindakshanpillai, P., Anu Aravind, Renu Pandey, Brijesh Kumar, Kumarapillai R. T. Asha, and Koranappallil B. Rameshkumar. 2016. “Phytochemical Screening of Garcinia Travancorica by HPLC-ESI-QTOF Mass Spectrometry and Cytotoxicity Studies of the Major Biflavonoid Fukugiside.” Natural Product Communications 11(12):1839–42.
Artasensi, Angelica., Alessandro. Pedretti, Giulio. Vistoli, and Laura. Fumagalli. 2020. “Type 2 Diabetes Mellitus: A Review of Multi-Target Drugs.” Molecules 25(8):1–20.
Ascaso, Juan F. 2014. “Diabetes Mellitus Tipo 2: Nuevos Tratamientos.” Medicina Clinica 143(3):117–23.
Aschner, P. 2010. “Diabetología.” Endocrinología, Diabetes y Nutrición 26(2):95–100.
Assemian, Inès Christelle., Alphonsine Chadon, Abdelhakim Bouyahya, Nadia Dakka, and Youssef Bakri. 2019. “Garcinia Mangostana Leaf Extracts from Ivory Coast Possess Remarkable Antioxidant, Anti-Inflammatory and Cytotoxicological Properties.” Biomedical and Pharmacology Journal 12(2):571–78.
Atanasov, Atanas G., Sergey B. Zotchev, Verena M. Dirsch, Ilkay Erdogan Orhan, Maciej Banach, Judith M. Rollinger, Davide Barreca, Wolfram Weckwerth, Rudolf Bauer, Edward A. Bayer, Muhammed Majeed, Anupam Bishayee, Valery Bochkov, Günther K. Bonn, Nady Braidy, Franz Bucar, Alejandro Cifuentes, Grazia D’Onofrio, Michael Bodkin, Marc Diederich, Albena T. Dinkova-Kostova, Thomas Efferth, Khalid El Bairi, Nicolas Arkells, Tai Ping Fan, Bernd L. Fiebich, Michael Freissmuth, Milen I. Georgiev, Simon Gibbons, Keith M. Godfrey, Christian W. Gruber, Jag Heer, Lukas A. Huber, Elena Ibanez, Anake Kijjoa, Anna K. Kiss, Aiping Lu, Francisco A. Macias, Mark J. S. Miller, Andrei Mocan, Rolf Müller, Ferdinando Nicoletti, George Perry, Valeria Pittalà, Luca Rastrelli, Michael Ristow, Gian Luigi Russo, Ana Sanches Silva, Daniela Schuster, Helen Sheridan, Krystyna Skalicka-Woźniak, Leandros Skaltsounis, Eduardo Sobarzo-Sánchez, David S. Bredt, Hermann Stuppner, Antoni Sureda, Nikolay T. Tzvetkov, Rosa Anna Vacca, Bharat B. Aggarwal, Maurizio Battino, Francesca Giampieri, Michael Wink, Jean Luc Wolfender, Jianbo Xiao, Andy Wai Kan Yeung, Gérard Lizard, Michael A. Popp, Michael Heinrich, Ioana Berindan-Neagoe, Marc Stadler, Maria Daglia, Robert Verpoorte, and Claudiu T. Supuran. 2021. “Natural Products in Drug Discovery: Advances and Opportunities.” Nature Reviews Drug Discovery 20(3):200–216.
Balasubramanian, Krishnamoorthi., and Krishnamoorthi. Rajagopalan. 1988. “Novel Xanthones from Garcinia Mangostana, Structures of BR-Xanthone-A and BR-Xanthone-B.” Phytochemistry 27(5):1552–54.
Ballester, María Salvat, and Giorgio Giorgi. 2017. “Diseño de Fármacos Multidiana.”
Bell, Joseph. 2006. “Treatment of Diabetes.” The American Journal of the Medical Sciences 64:497–503.
Birari, Rahul B., and Kamlesh K. Bhutani. 2007. “Pancreatic Lipase Inhibitors from Natural Sources: Unexplored Potential.” Drug Discovery Today 12(19–20):879–89.
Bisswanger, Hans. 2014. “Enzyme Assays.” Perspectives in Science 1(1–6):41–55.
Boonnak, Nawong, Suchada Chantrapromma, Supinya Tewtrakul, and Teeratad Sudsai. 2014. “Inhibition of Nitric Oxide Production in Lipopolysaccharide-Activated RAW264.7 Macrophages by Isolated Xanthones from the Roots of Cratoxylum Formosum Ssp. Pruniflorum.” Archives of Pharmacal Research 37(10):1329–35.
Brás, Natércia F., Diogo Santos-Martins, Pedro A. Fernandes, and Maria J. Ramos. 2018. “Mechanistic Pathway on Human α-Glucosidase Maltase-Glucoamylase Unveiled by QM/MM Calculations.” Journal of Physical Chemistry B 122(14):3889–99.
Briggyth, Katherine, Angélica María Rojas, and Marcela Castillo. 2019. “Inhibidores de La Lipasa Pancreática Como Alternativa de Tratamiento Frente a La Obesidad Inhibitors of Pancreatic Lipase as an Alternative of Treatment against Obesity ARTÍCULO ORIGINAL.” 7:23–30.
Brito, Lavínia de C., Ana Luiza Rangel Berenger, and Maria Raquel Figueiredo. 2017. “An Overview of Anticancer Activity of Garcinia and Hypericum.” Food and Chemical Toxicology 109:847–62.
Bustanji, Yasser, Ihab M. Al-Masri, Mohammad Mohammad, Mohammad Hudaib, Khaled Tawaha, Hamada Tarazi, and Hatim S. Alkhatib. 2011. “Pancreatic Lipase Inhibition Activity of Trilactone Terpenes of Ginkgo Biloba.” Journal of Enzyme Inhibition and Medicinal Chemistry 26(4):453–59.
Calderón S., José Víctor, Elvia Guadalupe Muñoz R., and Martha Angélica Quintanar E. 2013. “Estrés Oxidativo y Diabetes Mellitus.” Revista de Educación Bioquímica 32(2):54–66.
Chae, Hee Sung, Eun Young Kim, Ling Han, Na Rae Kim, Bunthoeun Lam, Jin Hyub Paik, Kee Dong Yoon, Young Hee Choi, and Young Won Chin. 2016. “Xanthones with Pancreatic Lipase Inhibitory Activity from the Pericarps of Garcinia Mangostana L. (Guttiferae).” European Journal of Lipid Science and Technology 118(9):1416–21.
Chantarasriwong, Oraphin, Bashayer D. Althufairi, Nicholas J. Checchia, and Emmanuel A. Theodorakis. 2018. “Caged Garcinia Xanthones: Synthetic Studies and Pharmacophore Evaluation.” Pp. 93–131 in Studies in Natural Products Chemistry. Vol. 58. Elsevier B.V.
Chaudhury, Arun, Chitharanjan Duvoor, Vijaya Dendi, Reddy Kraleti Sena, Aditya Chada Shashank, Rahul Ravilla, Asween Marco, Nawal Singh Shekhawat, Maria Theresa Montales, Kevin Kuriakose, Appalanaidu Sasapu, Alexandria Beebe, Naveen Patil, Chaitanya K. Musham Lohani, and Govinda Prasad Mirza. 2017. “Clinical Review of Antidiabetic Drugs: Implications for Type 2 Diabetes Mellitus Management.” Frontiers in Endocrinology 8(6):208–10.
Che Hassan, Nurul Khairina Najwa, Muhammad Taher, and Deny Susanti. 2018. “Phytochemical Constituents and Pharmacological Properties of Garcinia Xanthochymus- a Review.” Biomedicine and Pharmacotherapy 106(April):1378–89.
Chen, Lih Geeng, Ling Ling Yang, and Ching Chiung Wang. 2008. “Anti-Inflammatory Activity of Mangostins from Garcinia Mangostana.” Food and Chemical Toxicology 46(2):688–93.
Chintoju, Navajyothi, Prasanthi Konduru, Rajya Lakshmi Kathula, and Ravalli Remella. 2015. “Importance of Natural Products in the Modern History.” Research & Reviews: Journal of Hospital and Clinical Pharmacy 1(1):5–10.
Corbatón Anchuelo, A., R. Cuervo Pinto, and M. Serrano Ríos. 2004. “Diabetes Mellitus. Concepto, Clasificación y Mecanismos Etiopatogénicos.” Medicine - Programa de Formación Médica Continuada Acreditado 9(16):963–70.
Costa Gil, José Esteban, and Eduardo Spinedi. 2017. “La Tormentosa Relación Entre Las Grasas y El Desarrollo de La Diabetes Mellitus de Tipo 2: Actualizado. Parte 1.” Revista Argentina de Endocrinología y Metabolismo 1–15.
Cruz, Maria I. 2017. “Dual/Multitargeted Xanthone Derivatives for Alzheimer’s Disease: Where Do We Stand?” Future Medicinal Chemistry 9(14):1611–30.
Deachathai, S., W. Mahabusarakam, S. Phongpaichit, and W. C. Taylor. 2005. “Phenolic Compounds from the Fruit of Garcinia Dulcis.” Phytochemistry 66(19):2368–75.
Ernst, Heidi A., Leila Lo Leggio, Martin Willemoës, Gordon Leonard, Paul Blum, and Sine Larsen. 2006. “Structure of the Sulfolobus Solfataricus α-Glucosidase: Implications for Domain Conservation and Substrate Recognition in GH31.” Journal of Molecular Biology 358(4):1106–24.
Farrington, Rachael, Ian F. Musgrave, and Roger W. Byard. 2019. “Evidence for the Efficacy and Safety of Herbal Weight Loss Preparations.” Journal of Integrative Medicine (December 2018).
Fischer, André, Manuel Smiesko, Martin Sellner, and Markus A. Lill. 2020. “Decision Making in Structure-Based Drug Discovery: Visual Inspection of Docking Results ̌.” Journal of Medicinal Chemistry.
Fundación para la Diabetes, and Novo Nordisk. 2020. “2004: Diabetes y Obesidad.” 14 de Noviembre, Día Mundial de La
Diabetes 2004 21(1):1–9. Retrieved (https://www.fundaciondiabetes.org/diamundial/353/2004-diabetes-y-obesidad).
Gai-Li, Li, Cai Chao-Yun, He Jia-Yun, Li Rao, Lin Ma, Yan Liu, and Bo Wang. 2016. “Synthesis of 3-Acyloxyxanthone Derivatives as α-Glucosidase Inhibitors: A Further Insight into the 3-Substituents’ Effect.” Bioorganic and Medicinal Chemistry 24(7):1431–38.
García Martín, Pilar, and Margarita Vega Holm. 2018. “Pilar García Martín Fármacos Multidiana. Aplicaciones Terapéuticas.” Gendaram, Odontuya, Lai Daowan, Purevdorj Erdenetsogt, and Proksch Peter. 2017. “Pancreatic Lipase Inhibitory and Antioxidative Constituents from the Aerial Parts of Paeonia Lactiflora Pall. (Ranunculaceae).” Phytochemistry Letters 21(2017):240–46.
Genovese, Salvatore, Serena Fiorito, Vito Alessandro Taddeo, and Francesco Epifano. 2016. “Recent Developments in the Pharmacology of Prenylated Xanthones.” Drug Discovery Today 21(11):1814–19.
Gokaraju, Ganga. 2009. “Wo 2009/093259 A2.” (12).
Goodsell, David S., Garrett M. Morris, and Arthur J. Olson. 1996. “Automated Docking.” Journal of Molecular Recognition 9(November 1995):1–5.
Gorgojo-Martínez, J. J. 2014. “Nuevos Fármacos Antidiabéticos: Avanzando Hacia El Control Integral de La Diabesidad.” Hipertension y Riesgo Vascular 31(2):45–57.
Gu, Yeyi, William J. Hurst, David A. Stuart, and Joshua D. Lambert. 2011. “Inhibition of Key Digestive Enzymes by Cocoa Extracts and Procyanidins.” Journal of Agricultural and Food Chemistry 59(10):5305–11.
Ha, Ly Dieu, Poul Erik Hansen, Ole Vang, Fritz Duus, Hung Dinh Pham, and Lien Hoa Dieu Nguyen. 2009. “Cytotoxic Geranylated Xanthones and O-Alkylated Derivatives of α-Mangostin.” Chemical and Pharmaceutical Bulletin 57(8):830–34.
Han, Ah Reum, Jeong Ah Kim, Daniel D. Lantvit, Leonardus B. S. Kardono, Soedarsono Riswan, Heebyung Chai, Esperanza J. Carcach. De Blanco, Norman R. Farnsworth, Steven M. Swanson, and A. Douglas Kinghorn. 2009. “Cytotoxic Xanthone Constituents of the Stem Bark of Garcinia Mangostana (Mangosteen).” Journal of Natural Products 72(11):2028–31.
Hasenah, Ali., P. J. Houghton, and A. Soumyanath. 2006. “α-Amylase Inhibitory Activity of Some Malaysian Plants Used to Treat Diabetes; with Particular Reference to Phyllanthus Amarus.” Journal of Ethnopharmacology 107(3):449–55.
Hiếu, Nguyễn Trí, Hà Diệu Ly, Phạm Đình Hùng, and Nguyễn D. Liên Hoa. 2009. “Isolation and Structural Identification of Five Xanthone Derivatives from the Pericarps of Garcinia Mangostana L.” Tap Chi Duoc Hoc 48(8):18–22.
Ibrahim, Sabrin R. M., Hossam M. Abdallah, Ali M. El-Halawany, Mohammed F. Radwan, Ibrahim A. Shehata, Essam M. Al-Harshany, Mohamed F. Zayed, and Gamal A. Mohamed. 2018. “Garcixanthones B and C, New Xanthones from the Pericarps of Garcinia Mangostana and Their Cytotoxic Activity.” Phytochemistry Letters 25(March):12–16.
Ibrahim, Sabrin R. M., Gamal A. Mohamed, Maan T. Khayat, Sahar Ahmed, Hany Abo-Haded, and Khalid Z. Alshali. 2019. “Mangostanaxanthone VIIII, a New Xanthone from Garcinia Mangostana Pericarps, α-Amylase Inhibitory Activity, and Molecular Docking Studies.” Brazilian Journal of Pharmacognosy 29(2):206–12.
Islas Andrade, Sergio A., and María Cristina Revilla Monsalve. 2013. Diabetes Mellitus: Actualizaciones. S.E. edited by S. A. de C. V. Editorial Alfil. México D. F.
Ito, Chihiro, Masataka Itoigawa, Tomoko Takakura, Nijisiri Ruangrungsi, Fumio Enjo, Harukuni Tokuda, Hoyoku Nishino, and Hiroshi Furukawa. 2003. “Chemical Constituents of Garcinia Fusca: Structure Elucidation of Eight New Xanthones and Their Cancer Chemopreventive Activity.” Journal of Natural Products 66(2):200–205.
Iwai, Kunihisa, Mi Yeon Kim, Akio Onodera, and Hajime Matsue. 2006. “α-Glucosidase Inhibitory and Antihyperglycemic Effects of Polyphenols in the Fruit of Viburnum Dilatatum Thunb.” Journal of Agricultural and Food Chemistry 54(13):4588–92.
Ji, Xiuhong, Bharathi Avula, and Ikhlas A. Khan. 2007. “Quantitative and Qualitative Determination of Six Xanthones in Garcinia Mangostana L. by LC-PDA and LC-ESI-MS.” Journal of Pharmaceutical and Biomedical Analysis 43(4):1270–76.
Jiang, He Zhong, Xiao Fang Quan, Wei Xi Tian, Jiang Miao Hu, Peng Cheng Wang, Sheng Zhuo Huang, Zhong Quan Cheng, Wen Juan Liang, Jun Zhou, Xiao Feng Ma, and You Xing Zhao. 2010. “Fatty Acid Synthase Inhibitors of Phenolic Constituents Isolated from Garcinia Mangostana.” Bioorganic and Medicinal Chemistry Letters 20(20):6045–47.
Johnson, Philip J., Charles E. Wiedmeyer, Alison LaCarrubba, V. K. Ganjam, and Nat T. Messer IV. 2012. “Diabetes, Insulin Resistance,and Metabolic Syndrome in Horses.” Journal of Diabetes Science and Technology 6(3):534–40.
Keilany, Ziad. 2005. “Natural Products. Drug Discovery and Therapeu- Tic Medicine.” Review of Social Economy 36(2):228–29.
Khaw, K. Y., S. B. Choi, S. C. Tan, H. A. Wahab, K. L. Chan, and V. Murugaiyah. 2014. “Prenylated Xanthones from Mangosteen as Promising Cholinesterase Inhibitors and Their Molecular Docking Studies.” Phytomedicine 21(11):1303–9.
Kim, Jang Hoon, Hyo Young Kim, Seo Young Yang, Jin Baek Kim, Chang Hyun Jin, and Young Ho Kim. 2018. “Inhibitory Activity of (−)-Epicatechin-3,5-O-Digallate on α-Glucosidase and in Silico Analysis.” International Journal of Biological Macromolecules 107(PartA):1162–67.
Kulkarni, P. P., A. J. Kadam, R. B. Mane, Uday V. Desai, and P. P. Wadgaonkar. 1999. “Demethylation of Methyl Aryl Ethers Using Pyridine Hydrochloride in Solvent-Free Conditions under Microwave Irradiation.” Journal of Chemical Research 6(394–395):1–2.
Lanchero Barrios, Irvyng Patrick. 2016. “Irvyng Patrick Lanchero Barrios.” Universidad Nacional de Colombia (Tesis de maestría).
Le, My Phuong T., Miguel A. Lanaspa, Christina M. Cicerchi, Jatinder Rana, Jeffrey D. Scholten, Brandi L. Hunter, Christopher J. Rivard, R. Keith Randolph, and Richard J. Johnson. 2016. “Bioactivity-Guided Identification of Botanical Inhibitors of Ketohexokinase.” PLoS ONE 11(6):1–17.
Lee, Young A., Eun Ju Cho, Takashi Tanaka, and Takako Yokozawa. 2007. “Inhibitory Activities of Proanthocyanidins from Persimmon against Oxidative Stress and Digestive Enzymes Related to Diabetes.” Journal of Nutritional Science and Vitaminology 53(3):287–92.
Li, Huilin, Fengrui Song, Junpeng Xing, Rong Tsao, Zhiqiang Liu, and Shuying Liu. 2009. “Screening and Structural Characterization of α-Glucosidase Inhibitors from Hawthorn Leaf Flavonoids Extract by Ultrafiltration LC-DAD-MSnand SORI-CID FTICR MS.” Journal of the American Society for Mass Spectrometry 20(8):1496–1503.
Li, Jin, Ailing Fu, and Le Zhang. 2019. “An Overview of Scoring Functions Used for Protein–Ligand Interactions in Molecular Docking.” Interdisciplinary Sciences: Computational Life Sciences 11(2):320–28.
Li, Zuo Peng, Yeong Hun Song, Zia Uddin, Yan Wang, and Ki Hun Park. 2018. “Inhibition of Protein Tyrosine Phosphatase 1B (PTP1B) and α-Glucosidase by Xanthones from Cratoxylum Cochinchinense, and Their Kinetic Characterization.” Bioorganic and Medicinal Chemistry 26(3):737–46.
Libert, Diane M., Amy S. Nowacki, and Marvin R. Natowicz. 2018. “Metabolomic Analysis of Obesity, Metabolic Syndrome, and Type 2 Diabetes: Amino Acid and Acylcarnitine Levels Change along a Spectrum of Metabolic Wellness.” PeerJ 2018(8).
Lim, T. K. 2012. “Edible Medicinal and Non-Medicinal Plants: Volume 2, Fruits.” Edible Medicinal and Non-Medicinal Plants: Volume 2, Fruits 2:1–1088.
Liu, Qianyu, Dan Li, Anqi Wang, Zhen Dong, Sheng Yin, Qingwen Zhang, Yang Ye, Liangchun Li, and Ligen Lin. 2016. “Nitric Oxide Inhibitory Xanthones from the Pericarps of Garcinia Mangostana.” Phytochemistry 131:115–23.
López Vallejo, Fabián, José Luis Medina Franco, and Rafael Castillo. 2018. “Diseño de Fármacos Asistido Por Computadora.” Educación Química 17(4):452.
Mahendran, G., M. Manoj, K. J. Rajendra Prasad, and V. Narmatha Bai. 2015. “Antioxidants, Anti-Proliferative, Anti-Inflammatory, Anti-Diabetic and Anti-Microbial Effects of Isolated Compounds from Swertia Corymbosa (Grieb.) Wight Ex C.B. Clark – An in Vitro Approach.” Food Science and Human Wellness 4(4):169–79.
Marrelli, Mariangela, Monica Rosa Loizzo, Marcello Nicoletti, Francesco Menichini, and Filomena Conforti. 2013. “Inhibition of Key Enzymes Linked to Obesity by Preparations From Mediterranean Dietary Plants: Effects on α-Amylase and Pancreatic Lipase Activities.” Plant Foods for Human Nutrition 68(4):340–46.
Martínez Grau, M. ángeles, and Aurelio G. Csákÿ. 2012. Técnicas Experimentales En Síntesis Orgánica. Segunda ed. edited by S. A. EDITORIAL SÍNTESIS.
Medellín Zabala, Diana Marcela. 2016. “Sistemática Del Género Garcinia (Clusiaceae): Revisión Taxonómica Para Colombia y Filogenia de Las Especies Neotropicales.” Universidad Nacional de Colombia (Tesis de Maestría).
Medina-Franco, José L., Eli Fernán-Dezde Gortari, and J. Jesús Naveja. 2015. “Avances En El Diseño de Fármacos Asistido Por Computadora.” Educacion Quimica 26(3):180–86.
Mignani, Serge, Scot Huber, Helena Tomás, João Rodrigues, and Jean Pierre Majoral. 2016. “Why and How Have Drug Discovery Strategies in Pharma Changed? What Are the New Mindsets?” Drug Discovery Today 21(2):239–49.
Mohamed Ibrahim, Sabrin Ragab, Gamal Abdallah Mohamed, Maan Talaat Abdullah Khayat, Sahar Ahmed, and Hany Abo-Haded. 2019. “α-Amylase Inhibition of Xanthones from Garcinia Mangostana Pericarps and Their Possible Use for the Treatment of Diabetes with Molecular Docking Studies.” Journal of Food Biochemistry 43(5):1–9.
Morales Gómez, Angy Tatiana. 2017. “Determinación Del Potencial Inhibidor Del Extracto y Fracciones de Passiflora Manicata Sobre Enzimas Digestivas (α-Amilasa, α-Glucosidasa y Lipasa Pancreática).” Pontificia Universidad Javeriana (Tesis de Maestría).
Morelli, Carlo F., Marco Biagiotti, Valeria M. Pappalardo, Marco Rabuffetti, and Giovanna Speranza. 2015. “Chemistry of α-Mangostin. Studies on the Semisynthesis of Minor Xanthones from Garcinia Mangostana.” Natural Product Research 29(8):750–55.
Nagem, Tanus Jorge, and Fernando Faustino De Oliveira. 1997. “Xanthones and Other Constituents of Vismia Parviflora.” Journal of the Brazilian Chemical Society 8(5):505–8.
Neves, Bruno J., Rodolpho C. Braga, Cleber C. Melo-Filho, José Teófilo Moreira-Filho, Eugene N. Muratov, and Carolina Horta Andrade. 2018. “QSAR-Based Virtual Screening: Advances and Applications in Drug Discovery.” Frontiers in Pharmacology 9(NOV).
Newman, David J., and Gordon M. Cragg. 2020. “Natural Products as Sources of New Drugs over the Nearly Four Decades from 01/1981 to 09/2019.” Journal of Natural Products 83(3):770–803.
Nguyen, Chi N., Binh T. D. Trinh, Toan B. Tran, Le Thu T. Nguyen, Anna K. Jäger, and Lien Hoa D. Nguyen. 2017. “Anti-Diabetic Xanthones from the Bark of Garcinia Xanthochymus.” Bioorganic and Medicinal Chemistry Letters 27(15):3301–4. Nisha, J. 2017. “In-Silico Screening of Alpha Amylase Enzyme Inhibitors from Siddha Formulation Pungampoo Chooranam by Molecular Docking Analysis for the Management of Type II Diabetes Mellitus.” International Journal of Current Research in Medical Sciences 3(10):24–34.
Ochir, Sarangowa, Makoto Nishizawa, Byoung Jae Park, Kouta Ishii, Tsutomu Kanazawa, Minoru Funaki, and Takashi Yamagishi. 2010. “Inhibitory Effects of Rosa Gallica on the Digestive Enzymes.” Journal of Natural Medicines 64(3):275–80. Oda, Akifumi, Keiichi Tsuchida, Tadakazu Takakura, Noriyuki Yamaotsu, and Shuichi Hirono. 2006. “Comparison of Consensus Scoring Strategies for Evaluating Computational Models of Protein - Ligand Complexes.” 380–91.
OMS/OPS. 2017. “La Obesidad Entre Los Niños y Los Adolescentes Se Ha Multiplicado Por 10 En Los Cuatro Últimos Decenios.” Protección & Seguridad En La Comunidad 1–6. Retrieved (http://www.who.int/mediacentre/news/releases/2017/increase-childhood-obesity/es/).
OMS. 2013. Estrategia de Medicina Tradicional de La OMS 2014-2023. 1 edición. edited by Organización mundial de la salud and W. Chokwiwat.
OMS. 2018. “Obesidad y Sobrepeso.” Obesidad y Sobrepeso. Retrieved (http://www.who.int/es/news-room/fact-sheets/detail/obesity-and-overweight).
OPS/OMS Colombia. 2018. “OPS- Enfermedades No Transmitibles.Pdf.”
Palacio-Rodríguez, Karen, Isaias Lans, Claudio N. Cavasotto, and Pilar Cossio. 2019. “Exponential Consensus Ranking Improves the Outcome in Docking and Receptor Ensemble Docking.” Scientific Reports 9(1):1–14. Pappachan, Joseph M., Cornelius J. Fernandez, and Elias C. Chacko. 2019. “Diabesity and Antidiabetic Drugs.” Molecular Aspects of Medicine 66(August):3–12.
Pedraza-Chaverri, José, Noemí Cárdenas-Rodríguez, Marisol Orozco-Ibarra, and Jazmin M. Pérez-Rojas. 2008. “Medicinal Properties of Mangosteen (Garcinia Mangostana).” Food and Chemical Toxicology 46(10):3227–39.
Peres, Valdir, Tanus Jorge Nagem, and Fernando Faustino De Oliveira. 2000. “Tetraoxygenated Naturally Occurring Xanthones.” Phytochemistry 55(7):683–710.
Pérez-Sánchez, H., G. Cano, J. García-Rodríguez, and J. M. Cecilia. 2015. “Descubrimiento de Fármacos Basado En Cribado Virtual Refinado Con Enfoques Neuronales Paralelos.” Revista Internacional de Metodos Numericos Para Calculo y Diseno En Ingenieria 31(4):207–11.
Pierre Egloff, Marie, Frank Marguet, Gerard Buono, Robert Venger, Christian* Camillau, and Herman Von Tilbeurgho. 1995. “A Resolution Structure of the Pancreatic Lipase-Colipase Complex.” Biochemistry 34:2751–62.
Pleiss, Jürgen, Markus Fischer, Marcus Peiker, Claudia Thiele, and Rolf D. Schmid. 2000. “Lipase Engineering Database.” Journal of Molecular Catalysis B: Enzymatic 10(5):491–508.
Ponce, Jorge Orlando, Nazarena Rodriguez Vigay, and rolando pablo Juarez. 2019. “Inhibición α -Amilasa Por Medio de Extractos de Plantas Medicinales Como Tratamiento Complementario/Alternativo de La Diabetes y La Caries.” Revista de La Sociedad Odontolólgica de La Plata (SOLP) 55(May 2018):41–44.
Preto, Jordane, and Francesco Gentile. 2019. “Assessing and Improving the Performance of Consensus Docking Strategies Using the DockBox Package.” Journal of Computer-Aided Molecular Design 33(9):817–29.
Qian, Minxie, Silvia Spinelli, Hugues Driguez, and Françoise Payan. 1997. “Structure of a Pancreatic α-Amylase Bound to a Substrate Analogue at 2.03 Å Resolution.” Protein Science 6(11):2285–96.
Raksat, Achara, Piyaporn Phukhatmuen, Jianxiong Yang, Wisanu Maneerat, Rawiwan Charoensup, Raymond J. Andersen, Yan A. Wang, Stephen G. Pyne, and Surat Laphookhieo. 2020. “Phloroglucinol Benzophenones and Xanthones from the Leaves of Garcinia Cowa and Their Nitric Oxide Production and α-Glucosidase Inhibitory Activities.” Journal of Natural Products 83(1):164–68.
Raksat, Achara, Tawanun Sripisut, and Wisanu Maneerat. 2015. “Bioactive Xanthones from Cratoxylum Cochinchinense.” Natural Product Communications 10(11):1969–72.
Rao, P. Suryaprakasa, P. Prabhakara Reddy, and T. R. Seshadri. 1940. “Methylation of Hydroxy Flavonols Using Methyl Iodide and Potassium Carbonate.” Proceedings of the Indian Academy of Sciences - Section A 12(6):495–97.
Ren, Yulin, Susan Matthew, Daniel D. Lantvit, Tran Ngoc Ninh, Heebyung Chai, James R. Fuchs, Djaja D. Soejarto, Esperanza J. Carcach. De Blanco, Steven M. Swanson, and A. Douglas Kinghorn. 2011. “Cytotoxic and NF-ΚB Inhibitory Constituents of the Stems of Cratoxylum Cochinchinense and Their Semisynthetic Analogues.” Journal of Natural Products 74(5):1117–25.
Repasky, Matthew P., Mee Shelley, and Richard A. Friesner. 2007. “Flexible Ligand Docking with Glide.” Pp. 1–36 in Current Protocols in Bioinformatics.
Rodriguez, E., J. M. Perea, A. M. Ortega, and R. M. López-sobaler. 2009. “Obesidad, Resistencia a La Insulina y Aumento de Los Niveles de Adipoquinas: Importancia de La Dieta y El Ejercicio Físico.” Nutrición Hospitalaria 24(4):415–21.
Ryu, Hyung Won, Jung Keun Cho, Marcus J. Curtis-Long, Heung Joo Yuk, Young Soo Kim, Sunin Jung, Young Suk Kim, Byong
Won Lee, and Ki Hun Park. 2011. “α-Glucosidase Inhibition and Antihyperglycemic Activity of Prenylated Xanthones from Garcinia Mangostana.” Phytochemistry 72(17):2148–54.
Saboury, A. A. 2009. “Enzyme Inhibition and Activation: A General Theory.” Journal of the Iranian Chemical Society 6(2):219–29.
Salud, Ministerio de. 2005. Guía de Atención de La Obesidad. Bogotá D. C.
Salvador Rodríguez, J., C. Abreu Padín, F. Rotellar Sastre, and G. Frühbeck Martínez. 2004. “Tratamiento de La Obesidad. Medidas de Estilo de Vida y Régimen Alimentario. Tratamiento Farmacológico. Tratamiento Quirúrgico.” Medicine - Programa de Formación Médica Continuada Acreditado 9(19):1176–85.
Sankar, Veintramuthu, and S. .. Maida Engels. 2018. “Synthesis, Biological Evaluation, Molecular Docking and in Silico ADME Studies of Phenacyl Esters of N-Phthaloyl Amino Acids as Pancreatic Lipase Inhibitors.” Future Journal of Pharmaceutical Sciences 4(2):276–83.
Santos, Clementina M. M., Marisa Freitas, and Eduarda Fernandes. 2018. “A Comprehensive Review on Xanthone Derivatives as α-Glucosidase Inhibitors.” European Journal of Medicinal Chemistry 157:1460–79.
Sassaki, Guilherme L., Marcello Iacomini, and Philip A. J. Gorin. 2005. “Methylation-GC-MS Analysis of Arabinofuranose- And Galactofuranose- Containing Structures: Rapid Synthesis of Partially O-Methylated Alditol Acetate Standards.” Anais Da Academia Brasileira de Ciencias 77(2):223–34.
Sekhon-Loodu, Satvir, and H. P. Vasanth. Rupasinghe. 2019. “Evaluation of Antioxidant, Antidiabetic and Antiobesity Potential of Selected Traditional Medicinal Plants.” Frontiers in Nutrition 6.
Shakoor, Hira, Fatima Abdelfattah, Khaula Albadi, Mentalla Adib, Jaleel Kizhakkayil, and Carine Platat. 2020. “Inhibition of Digestive Enzyme and Stimulation of Human Liver Cells (HepG2) Glucose Uptake by Date Seeds Extract.” Evidence-Based Complementary and Alternative Medicine 2020.
Shang, Erchang, Yaxia Yuan, Xinyi Chen, Ying Liu, Jianfeng Pei, and Luhua Lai. 2014. “De Novo Design of Multitarget Ligands with an Iterative Fragment-Growing Strategy.” Journal of Chemical Information and Modeling 54(4):1235–41.
Da Silva, Franck, Jeremy Desaphy, and Didier Rognan. 2018. “IChem: A Versatile Toolkit for Detecting, Comparing, and Predicting Protein–Ligand Interactions.” ChemMedChem 13(6):507–10.
Sim, Lyann, Roberto Quezada-Calvillo, Erwin E. Sterchi, Buford L. Nichols, and David R. Rose. 2008. “Human Intestinal Maltase-Glucoamylase: Crystal Structure of the N-Terminal Catalytic Subunit and Basis of Inhibition and Substrate Specificity.” Journal of Molecular Biology 375(3):782–92.
Sriyatep, Teerayut, Ittipon Siridechakorn, Wisanu Maneerat, Acharavadee Pansanit, Thunwadee Ritthiwigrom, Raymond J. Andersen, and Surat Laphookhieo. 2015. “Bioactive Prenylated Xanthones from the Young Fruits and Flowers of Garcinia Cowa.” Journal of Natural Products 78(2):265–71.
Sriyatep, Teerayut, Cholpisut Tantapakul, Raymond J. Andersen, Brian O. Patrick, Stephen G. Pyne, Chatchai Muanprasat, Sawinee Seemakhan, Suparerk Borwornpinyo, and Surat Laphookhieo. 2018. “Resolution and Identification of Scalemic Caged Xanthones from the Leaf Extract of Garcinia Propinqua Having Potent Cytotoxicities against Colon Cancer Cells.” Fitoterapia 124(October):34–41.
Sudta, Pichit, Payung Jiarawapi, Apichart Suksamrarn, Poonpilas Hongmanee, and Sunit Suksamrarn. 2013. “Potent Activity against Multidrug-Resistant Mycobacterium Tuberculosis of α-Mangostin Analogs.” Chemical and Pharmaceutical Bulletin 61(2):194–203.
Sukandar, Edwin Risky, Sutin Kaennakam, Kitiya Rassamee, Taslim Ersam, Pongpun Siripong, and Santi Tip-Pyang. 2019. “Tetrandraxanthones A-I, Prenylated and Geranylated Xanthones from the Stem Bark of Garcinia Tetrandra.” Journal of Natural Products 82(5):1312–18.
Sukandar, Edwin Risky, Sutin Kaennakam, Kitiya Rassamee, Pongpun Siripong, Sri Fatmawati, Taslim Ersam, and Santi Tip-pyang. 2018. “Xanthones and Biphenyls from the Stems of Garcinia Cylindrocarpa and Their Cytotoxicity.” Fitoterapia 130(August):112–17.
Sultanbawa, M. U. S. 1980. “Xanthonoids of Tropical Plants.” Tetrahedron 36(11):1465–1506.
Sumaryada, T., and A. W. Roslia. 2016. “Molecular Docking Simulation of Mangostin Derivatives and Curcuminoid on Maltase- Glucoamylase Target for Searching Anti-Diabetes Drug Candidates.” 1st International Conference on Biomedical Engineering (IBIOMED, 1–4.
Taha, Muhammad, Nor Hadiani Ismail, Kulsoom Javaid, Syahrul Imran, El Hassane Anouar, Abdul Wadood, Atia-Tul-Wahab, Muhammad Ali, Khalid Mohammed Khan, Syed Muhammad Saad, Fazal Rahim, and M. Iqbal Choudhary. 2015. “Evaluation of 2-Indolcarbohydrazones as Potent α-Glucosidase Inhibitors, in Silico Studies and DFT Based Stereochemical Predictions.” Bioorganic Chemistry 63:24–35.
Torres R, Eugenio, Manuel Almeida S, and Christian Vogel. 2015. “Síntesis y Evaluación de La Actividad Antitumoral in Vitro de Un Éster Prenilado Análogo a Productos Naturales.” Química Viva 14(1):111–19.
Trott, Oleg, and Arthur J. Olson. 2012. “Software News and Update AutoDock Vina: Improving the Speed and Accuracy of Docking with a New Scoring Function, Efficient Optimization, and Multithreading.” Journal of Computational Chemistry 32:174–82.
Tusevski, Oliver, Branka Vinterhalter, Dijana Krstić Milošević, Marina Soković, Ana Ćirić, Dragan Vinterhalter, Snežana Zdravković Korać, Jasmina Petreska Stanoeva, Marina Stefova, and Sonja Gadzovska Simic. 2017. “Production of Phenolic Compounds, Antioxidant and Antimicrobial Activities in Hairy Root and Shoot Cultures of Hypericum Perforatum L.” Plant Cell, Tissue and Organ Culture 128(3):589–605.
Ubukata, Makoto, Hitomi Takamori, Misaki Ohashi, Shinya Mitsuhashi, Kaoru Yamashita, Tomohisa Asada, Noriyuki Nakajima, Nobuyasu Matsuura, Mie Tsuruga, Keiko Taki, and Junji Magae. 2007. “Mycophenolic Acid as a Latent Agonist of PPARγ.” Bioorganic and Medicinal Chemistry Letters 17(17):4767–70.
Uthuppan, Jasmine, and K. Soni. 2013. “Conformational Analysis: A Review.” International Journal of Pharmaceutical Sciences & … 4(1):34–41.
Veeramachaneni, Ganesh Kumar, K. Kranthi Raj, Leela Madhuri Chalasani, Sai Krishna Annamraju, JS Bondili, and Venkateswara Talluri. 2015. “Shape Based Virtual Screening and Molecular Docking towards Designing Novel Pancreatic Lipase Inhibitors.” Bioinformation 11(12):535–42.
Villarroya, Francesc. 2016. “Bioquimica De La Obesidad.” Sociedad Española de Bioquímica y Biología Molecular 190:28.
Vongsak, Boonyadist, Sumet Kongkiatpaiboon, Sunan Jaisamut, Sasipawan Machana, and Chamnan Pattarapanich. 2015. “In Vitro Alpha Glucosidase Inhibition and Free-Radical Scavenging Activity of Propolis from Thai Stingless Bees in Mangosteen Orchard.” Brazilian Journal of Pharmacognosy 25(5):445–50.
Walker, Edward B. 2007. “HPLC Analysis of Selected Xanthones in Mangosteen Fruit.” Journal of Separation Science 30(9):1229–34.
Wang, Jing J., Qing H. Shi, Wei Zhang, and Barbara J. S. Sanderson. 2012. “Anti-Skin Cancer Properties of Phenolic-Rich Extract from the Pericarp of Mangosteen (Garcinia Mangostana Linn.).” Food and Chemical Toxicology 50(9):3004–13.
Wang, Ming Hui, Kuo Jun ZHANG, Qin Lan GU, Xiao Ling BI, and Jin Xin WANG. 2017. “Pharmacology of Mangostins and Their Derivatives: A Comprehensive Review.” Chinese Journal of Natural Medicines 15(2):81–93.
Wang, Zerong. 2010. “Irvine-Purdie Methylation.” Comprehensive Organic Name Reactions and Reagents 1526–29.
Whitcomb, David C., and Mark E. Lowe. 2007. “Human Pancreatic Digestive Enzymes.” Digestive Diseases and Sciences 52(1):1–17.
Williams, John A. 2017. “Amylase.” Pancreapedia 1.
Williams, L. K., C. Li, S. G. Withers, and G. D. Brayer. 2012. “Order and Disorder: Differential Structural Impacts of Myricetin and Ethyl Caffeate on Human Amylase, an Antidiabetic Target.” J.Med.Chem. 55(101):77–86.
Xu, Youjun, Shiwei Wang, Qiwan Hu, Shuaishi Gao, Xiaomin Ma, Weilin Zhang, Yihang Shen, Fangjin Chen, Luhua Lai, and Jianfeng Pei. 2018. “CavityPlus: A Web Server for Protein Cavity Detection with Pharmacophore Modelling, Allosteric Site Identification and Covalent Ligand Binding Ability Prediction.” Nucleic Acids Research 46(W1):W374–79.
Yang, Hye Won, K. H. N. Fernando, Jae Young Oh, Xining Li, You Jin Jeon, and Bo Mi Ryu. 2019. “Anti-Obesity and Anti-Diabetic Effects of Ishige Okamurae.” Marine Drugs 17(4):1–11.
Ye, Gao Jie, Tian Lan, Zhi Xin Huang, Xiao Ning Cheng, Chao Yun Cai, Sen Miao Ding, Min Li Xie, and Bo Wang. 2019. “Design and Synthesis of Novel Xanthone-Triazole Derivatives as Potential Antidiabetic Agents: α-Glucosidase Inhibition and Glucose Uptake Promotion.” European Journal of Medicinal Chemistry 177:362–73.
Yeong, Keng Yoon, Kooi Yeong Khaw, Yukari Takahashi, Yukihiro Itoh, Vikneswaran Murugaiyah, and Takayoshi Suzuki. 2020. “Discovery of Gamma-Mangostin from Garcinia Mangostana as a Potent and Selective Natural SIRT2 Inhibitor.” Bioorganic Chemistry 94(June):103403.
Yuan, Haidan, Qianqian Ma, Li Ye, and Guangchun Piao. 2016. “The Traditional Medicine and Modern Medicine from Natural Products.” Molecules 21(5).
Zawawi, Nik Khairunissa Nik Abdullah, Muhammad Taha, Norizan Ahmat, Abdul Wadood, Nor Hadiani Ismail, Fazal Rahim, Syed Sikander Azam, and Noraishah Abdullah. 2016. “Benzimidazole Derivatives as New α-Glucosidase Inhibitors and in Silico Studies.” Bioorganic Chemistry 64:29–36.
Zhang, Bao Jun, Wen Wei Fu, Rong Wu, Jin Ling Yang, Cai Yun Yao, Bing Xiong Yan, Hong Sheng Tan, Chang Wu Zheng, Zhi Jun Song, and Hong Xi Xu. 2019. “Cytotoxic Prenylated Xanthones from the Leaves of Garcinia Bracteata.” Planta Medica 85(6):444–52.
Zhang, Weilin, Jianfeng Pei, and Luhua Lai. 2017. “Computational Multitarget Drug Design.” Journal of Chemical Information and Modeling 57(3):403–12.
Zhang, Yaozheng, Zhijun Song, Jing Hao, Shengxiang Qiu, and Zhifang Xu. 2010. “Two New Prenylated Xanthones and a New Prenylated Tetrahydroxanthone from the Pericarp of Garcinia Mangostana.” Fitoterapia 81(6):595–99.
Zheng, Guo qiang, Patrick M. Kenney, and Luke K. T. Lam. 1992. “Myristicin: A Potential Cancer Chemopreventive Agent from Parsley Leaf Oil.” Journal of Agricultural and Food Chemistry 40(1):107–10.
Zheng, Huan Huan, Cui Ting Luo, Heru Chen, Juan Na Lin, Chun Ling Ye, Shuang Shuang Mao, and Yu Lin Li. 2014. “Xanthones from Swertia Mussotii as Multitarget-Directed Antidiabetic Agents.” ChemMedChem 9(7):1374–77.
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spelling Atribución-NoComercial-SinDerivadas 4.0 InternacionalDerechos reservados al autor, 2021http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Patiño Ladino, Oscar Javiereaeddefce9dfa9681674dc4eb92a86d0Lopez Vallejo, Fabian Harveyeb85da1ee8ee772549861f7038b326dcCardozo Muñoz, Juan Camilo38a9e2c23086f9d8cb0d132850830612600Productos Naturales Vegetales Bioactivos y Quimica EcoIogica2021-08-18T15:44:10Z2021-08-18T15:44:10Z2021-08-17https://repositorio.unal.edu.co/handle/unal/79963Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/ilustraciones, fotografías, gráficas, tablasGarcinia mangostana (Clusiaceae), conocida popularmente como mangostino, es una especie de importancia económica a nivel mundial que se caracteriza por contener una amplia diversidad de xantonas, las cuales tienen la capacidad de inhibir enzimas digestivas como α-amilasa (AA), α-glucosidasa (AG) y lipasa pancreática (LP). Estas enzimas juegan un papel importante en el metabolismo de carbohidratos y lípidos, por lo que suelen ser atractivas dianas terapéuticas para el tratamiento de la diabetes tipo 2 y la obesidad. Existe una estrecha correlación entre estas dos enfermedades, por lo que en las últimas décadas muchas investigaciones se han enfocado en la búsqueda de moléculas con acción polifuncional para tratar de manera simultánea estas dos patologías. En este sentido, G. mangostana es un objeto interesante de estudios debido a que varios de sus componentes químicos causan inhibiciones en diferentes enzimas digestivas. La presente investigación contribuye a la búsqueda de moléculas con potencial inhibitorio multidiana frente a lipasa pancreática, α-amilasa y α-glucosidasa, a partir de un estudio de las xantonas provenientes de G. mangostana. La metodología incluyó el estudio fitoquímico biodirigido sobre el pericarpio de los frutos de G. mangostana, para aislar e identificar una serie de xantonas con potencial inhibidor sobre las enzimas diana de interés. Adicionalmente, se realizó la síntesis de algunos derivados a partir del constituyente mayoritario. Posteriormente, se determinó la concentración inhibitoria, el tipo de inhibición y el modo de unión que ejercen las xantonas sobre las enzimas digestivas. Finalmente, se realizó un estudio de optimización farmacodinámica con cada blanco enzimático tomando como base la molécula α-mangostina, para predecir posibles moléculas con acción multidiana y mayor afinidad frente a LP, AG y AA. Se realizó la síntesis de algunas de las moléculas optimizadas y se determinó el efecto que ejercen sobre las enzimas digestivas. El estudio químico biodirigido permitió determinar que en la fracción de DCM se concentra la actividad inhibitoria sobre las tres enzimas digestivas (LP, AG y AA). A partir de la fracción de DCM se logró el aislamiento e identificación de cinco xantonas preniladas, entre las que se encuentran 9-hidroxicalabaxantona (Gm-1), 8-desoxigartanina (Gm-2), gartanina (Gm-3), α-mangostina (Gm-4) y γ-mangostina (Gm-5). Adicionalmente, a partir del constituyente mayoritario Gm-4 se sintetizaron los derivados Gm-6 a Gm-11, destacándose la propuesta de una nueva metodología libre de disolvente y por irradiación con microondas para la obtención de compuestos aromáticos con ciclo tetrahidropirano, a partir de precursores aromáticos hidroxilados con una cadena prenilada vecinal. Entre los compuestos aislados y sintetizados se destacan Gm-4 (CI50 AA = 317,6 ± 4,3 μM, CI50 AG = 31,6 ± 2,6 µM y CI50 LP = 50,6 ± 6,7 μM) y Gm-6 (CI50 AA = 164,4 ± 28,6 μM, CI50 AG = 33,3 ± 4,1 µM y CI50 LP = 69,2 ± 6,9 μM) por su mayor acción multidiana sobre las tres enzimas. De manera general, con los estudios de cinética enzimática y de acoplamiento molecular, se encontró que las xantonas bioactivas ejercen su acción sobre AA en su mayoría mediante una inhibición de tipo competitivo, mientras que sobre AG predomina la inhibición de tipo mixto, y frente a LP la mayoría de los inhibidores son de tipo no competitivo. Por último, el estudio optimización farmacodinámica sobre Gm-4 permitió proponer 10 moléculas optimizadas, de las cuales se sintetizaron tres sin reportes previos en la literatura y que fueron denominadas como Gm-12, Gm-13 y Gm-14. Estas moléculas presentaron acción inhibitoria frente a LP, AG y AA, destacándose Gm-14 por su acción inhibitoria polifuncional, y por ser el único compuesto con el que se logró optimizar de manera simultánea la actividad inhibitoria frente a AG y AA. Adicionalmente, se estableció que los compuestos optimizados son de tipo competitivo para AA, de tipo no competitivo para AG, y no competitivo y acompetitivo para la enzima LP. (Texto tomado de la fuente)Garcinia mangostana (Clusiaceae), popularly known as mangosteen, is a species of economic importance worldwide that is characterized by containing a wide variety of xanthones, which can inhibit digestive enzymes such as α-amylase (AA), α- glucosidase (AG) and pancreatic lipase (LP). These enzymes play an important role in carbohydrate and lipid metabolism and are therefore often attractive therapeutic targets for the treatment of type 2 diabetes and obesity. There is a close correlation between these two diseases, reason why in the last decades many investigations have focused on the search for molecules with multitarget action to treat these two diseases simultaneously. In this sense, G. mangostana is an interesting object of study because several of its chemical components cause inhibitions in different digestive enzymes. The present investigation contributes to the search of molecules with multitarget inhibitory potential against pancreatic lipase, α-amylase and α-glucosidase, based on a study of xanthones from G. mangostana. The methodology included the bioguiated phytochemical study on the pericarp of G. mangostana fruits, to isolate and identify a series of xanthones with inhibitory potential on the target enzymes of interest. Additionally, some derivatives were synthesized from the majority constituent. Subsequently, the inhibitory concentration, the type of inhibition and the binding mode exerted by xanthones on digestive enzymes were determined. Finally, a pharmacodynamic optimization study was carried out with each target enzyme based on the α-mangostin molecule, to predict possible molecules with multitarget action and higher affinity against LP, AG and AA. The synthesis of some of the optimized molecules was carried out and the effect they exert on digestive enzymes was determined. The bioguiated chemical study made it possible to determine that the inhibitory activity on the three digestive enzymes (LP, AG and AA) is concentrated in the DCM fraction. From the DCM fraction, the isolation and identification of five prenylated xanthones was achieved, among which are 9-hydroxylabaxanthone (Gm-1), 8-deoxygartanine (Gm-2), gartanine (Gm-3), α- mangostin (Gm-4) and γ-mangostin (Gm-5). Additionally, from the majority constituent Gm-4, the derivatives Gm-6 to Gm-11 were synthesized, highlighting the proposal of a new solvent-free methodology with microwave irradiation for obtaining aromatic compounds with tetrahydropyran cycle, from hydroxylated aromatic precursors with a neighboring prenylated chain. Among the isolated and synthesized compounds, Gm-4 (IC50 AA = 317.6 ± 4.3 μM, IC50 AG = 31.6 ± 2.6 µM and IC50 LP = 50.6 ± 6.7 μM) and Gm-6 (IC50 AA = 164.4 ± 28.6 µM, IC50 AG = 33.3 ± 4.1 µM and IC50 LP = 69.2 ± 6.9 µM) due to its greater multitarget action on the three enzymes. In general, with the enzymatic kinetics and molecular coupling studies, it was found that bioactive xanthones exert their action on AA mostly through competitive inhibition, while on AG mixed-type inhibition predominates, and against LP most of inhibitors are non-competitive. Finally, the pharmacodynamic optimization study on Gm-4 allowed proposing 10 optimized molecules, of which three were synthesized without previous reports in the literature and which were called Gm-12, Gm-13 and Gm-14. These molecules showed inhibitory action against LP, AG and AA, with Gm-14 standing out for its polyfunctional inhibitory action, and for being the only compound with which it was possible to simultaneously optimize the inhibitory activity against AG and AA. Additionally, it was established that the optimized compounds are competitive inhibitors against AA, non-competitive for AG and non-competitive and uncompetitive for the LP enzyme. (Text taken from source)Apoyo financiero del Ministerio de Ciencia, Tecnología e Innovación (MinCiencias) a través del contrato 003-2017 con código 110174559038, financiado a través de la convocatoria nacional de proyectos para el fortalecimiento de la investigación, creación e innovación de la universidad nacional de Colombia 2016-2018. Apoyo al Joven Talento Juan Camilo Cardozo-Muñoz a través del contrato 907-2019 de la convocatoria 850-2019 para el fortalecimiento de proyectos de investigación de CTeI en ciencias médicas y de la salud con talento joven e impacto regional.MaestríaMagíster en Ciencias - QuímicaBioprospección en agentes fitosanitarios y terapéuticos158 páginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Ciencias - Maestría en Ciencias - QuímicaDepartamento de QuímicaFacultad de CienciasBogotá, ColombiaUniversidad Nacional de Colombia - Sede Bogotá540 - Química y ciencias afinesDiabetes Mellitus Tipo 2Diabetes Mellitus, Type 2ObesidadObesityLipasa pancreáticaα-amilasaα-glucosidasaXantonasG. mangostana.Pancreatic lipaseα-amylaseα-glucosidaseGarcinia mangostana.Estudio del potencial inhibitorio de las xantonas provenientes de Garcinia mangostana (Clusiaceae) sobre tres enzimas digestivas relacionadas con obesidad y diabetes tipo 2 en búsqueda de moléculas con acción multidianaStudy of the inhibitory potential of xanthones from Garcinia mangostana (Clusiaceae) on three digestive enzymes related to obesity and type 2 diabetes in search of molecules with multitarget actionTrabajo de grado - Maestríainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TMAbarca-Gómez, L., Z. A. Abdeen, Z. A. Hamid, N. M. Abu-Rmeileh, B. Acosta-Cazares, C. Acuin, and C. Agyemang. 2017. “Worldwide Trends in Body-Mass Index, Underweight, Overweight, and Obesity from 1975 to 2016: A Pooled Analysis of 2416 Population-Based Measurement Studies in 128·9 Million Children, Adolescents, and Adults.” The Lancet 390(10113):2627–42.Adnyana, I., A. Abuzaid, E. Iskandar, and N. Kurniati. 2016. “Pancreatic Lipase and α-Amylase Inhibitory Potential of Mangosteen ( Garcinia Mangostana Linn.) Pericarp Extract.” International Journal of Medical Research & Health Sciences 5(1):23.Aguilar S., Carlos A., and Pablo. Aschner. 2019. “Guías ALAD Sobre El Diagnóstico, Control y Tratamiento de La Diabetes Mellitus Tipo 2 Con Medicina Basada En Evidencia Edición 2019.” Revista de La Asociación Latinoamericana de Diabetes.Ah-Reum, Han, Jeong-Ah Kim, Daniel D. Lantvit, Leonarduz B. Kardonom, Soerdanoso Rsiwan, Heebyung Chai, Esperanza J. Carchate de blanco, Norman R. Farnsworth, Steven M. Swanson, and A. Douglas Kinghorn. 2009. “Cytotoxic Xanthone Constituents of the Stem Bark of Garcinia Mangostana (Mangosteen).” Journal of Natural Products 72(11):1–7.Al-Goblan, Abdullah S., Mohammed A. Al-Alfi, and Muhammad Z. Khan. 2014. “Mechanism Linking Diabetes Mellitus and Obesity.” Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 7:587–91.Alqahtani, Ali S., Syed Hidayathulla, Md Tabish Rehman, Ali A. Elgamal, Shaza Al-Massarani, Valentina Razmovski-Naumovski, Mohammed S. Alqahtani, Rabab A. El Dib, and Mohamed F. Alajmi. 2020. “Alpha-Amylase and Alpha-Glucosidase Enzyme Inhibition and Antioxidant Potential of 3-Oxolupenal and Katononic Acid Isolated from Nuxia Oppositifolia.” Biomolecules 10(1).Aravindakshanpillai, P., Anu Aravind, Renu Pandey, Brijesh Kumar, Kumarapillai R. T. Asha, and Koranappallil B. Rameshkumar. 2016. “Phytochemical Screening of Garcinia Travancorica by HPLC-ESI-QTOF Mass Spectrometry and Cytotoxicity Studies of the Major Biflavonoid Fukugiside.” Natural Product Communications 11(12):1839–42.Artasensi, Angelica., Alessandro. Pedretti, Giulio. Vistoli, and Laura. Fumagalli. 2020. “Type 2 Diabetes Mellitus: A Review of Multi-Target Drugs.” Molecules 25(8):1–20.Ascaso, Juan F. 2014. “Diabetes Mellitus Tipo 2: Nuevos Tratamientos.” Medicina Clinica 143(3):117–23.Aschner, P. 2010. “Diabetología.” Endocrinología, Diabetes y Nutrición 26(2):95–100.Assemian, Inès Christelle., Alphonsine Chadon, Abdelhakim Bouyahya, Nadia Dakka, and Youssef Bakri. 2019. “Garcinia Mangostana Leaf Extracts from Ivory Coast Possess Remarkable Antioxidant, Anti-Inflammatory and Cytotoxicological Properties.” Biomedical and Pharmacology Journal 12(2):571–78.Atanasov, Atanas G., Sergey B. Zotchev, Verena M. Dirsch, Ilkay Erdogan Orhan, Maciej Banach, Judith M. Rollinger, Davide Barreca, Wolfram Weckwerth, Rudolf Bauer, Edward A. Bayer, Muhammed Majeed, Anupam Bishayee, Valery Bochkov, Günther K. Bonn, Nady Braidy, Franz Bucar, Alejandro Cifuentes, Grazia D’Onofrio, Michael Bodkin, Marc Diederich, Albena T. Dinkova-Kostova, Thomas Efferth, Khalid El Bairi, Nicolas Arkells, Tai Ping Fan, Bernd L. Fiebich, Michael Freissmuth, Milen I. Georgiev, Simon Gibbons, Keith M. Godfrey, Christian W. Gruber, Jag Heer, Lukas A. Huber, Elena Ibanez, Anake Kijjoa, Anna K. Kiss, Aiping Lu, Francisco A. Macias, Mark J. S. Miller, Andrei Mocan, Rolf Müller, Ferdinando Nicoletti, George Perry, Valeria Pittalà, Luca Rastrelli, Michael Ristow, Gian Luigi Russo, Ana Sanches Silva, Daniela Schuster, Helen Sheridan, Krystyna Skalicka-Woźniak, Leandros Skaltsounis, Eduardo Sobarzo-Sánchez, David S. Bredt, Hermann Stuppner, Antoni Sureda, Nikolay T. Tzvetkov, Rosa Anna Vacca, Bharat B. Aggarwal, Maurizio Battino, Francesca Giampieri, Michael Wink, Jean Luc Wolfender, Jianbo Xiao, Andy Wai Kan Yeung, Gérard Lizard, Michael A. Popp, Michael Heinrich, Ioana Berindan-Neagoe, Marc Stadler, Maria Daglia, Robert Verpoorte, and Claudiu T. Supuran. 2021. “Natural Products in Drug Discovery: Advances and Opportunities.” Nature Reviews Drug Discovery 20(3):200–216.Balasubramanian, Krishnamoorthi., and Krishnamoorthi. Rajagopalan. 1988. “Novel Xanthones from Garcinia Mangostana, Structures of BR-Xanthone-A and BR-Xanthone-B.” Phytochemistry 27(5):1552–54.Ballester, María Salvat, and Giorgio Giorgi. 2017. “Diseño de Fármacos Multidiana.”Bell, Joseph. 2006. “Treatment of Diabetes.” The American Journal of the Medical Sciences 64:497–503.Birari, Rahul B., and Kamlesh K. Bhutani. 2007. “Pancreatic Lipase Inhibitors from Natural Sources: Unexplored Potential.” Drug Discovery Today 12(19–20):879–89.Bisswanger, Hans. 2014. “Enzyme Assays.” Perspectives in Science 1(1–6):41–55.Boonnak, Nawong, Suchada Chantrapromma, Supinya Tewtrakul, and Teeratad Sudsai. 2014. “Inhibition of Nitric Oxide Production in Lipopolysaccharide-Activated RAW264.7 Macrophages by Isolated Xanthones from the Roots of Cratoxylum Formosum Ssp. Pruniflorum.” Archives of Pharmacal Research 37(10):1329–35.Brás, Natércia F., Diogo Santos-Martins, Pedro A. Fernandes, and Maria J. Ramos. 2018. “Mechanistic Pathway on Human α-Glucosidase Maltase-Glucoamylase Unveiled by QM/MM Calculations.” Journal of Physical Chemistry B 122(14):3889–99.Briggyth, Katherine, Angélica María Rojas, and Marcela Castillo. 2019. “Inhibidores de La Lipasa Pancreática Como Alternativa de Tratamiento Frente a La Obesidad Inhibitors of Pancreatic Lipase as an Alternative of Treatment against Obesity ARTÍCULO ORIGINAL.” 7:23–30.Brito, Lavínia de C., Ana Luiza Rangel Berenger, and Maria Raquel Figueiredo. 2017. “An Overview of Anticancer Activity of Garcinia and Hypericum.” Food and Chemical Toxicology 109:847–62.Bustanji, Yasser, Ihab M. Al-Masri, Mohammad Mohammad, Mohammad Hudaib, Khaled Tawaha, Hamada Tarazi, and Hatim S. Alkhatib. 2011. “Pancreatic Lipase Inhibition Activity of Trilactone Terpenes of Ginkgo Biloba.” Journal of Enzyme Inhibition and Medicinal Chemistry 26(4):453–59.Calderón S., José Víctor, Elvia Guadalupe Muñoz R., and Martha Angélica Quintanar E. 2013. “Estrés Oxidativo y Diabetes Mellitus.” Revista de Educación Bioquímica 32(2):54–66.Chae, Hee Sung, Eun Young Kim, Ling Han, Na Rae Kim, Bunthoeun Lam, Jin Hyub Paik, Kee Dong Yoon, Young Hee Choi, and Young Won Chin. 2016. “Xanthones with Pancreatic Lipase Inhibitory Activity from the Pericarps of Garcinia Mangostana L. (Guttiferae).” European Journal of Lipid Science and Technology 118(9):1416–21.Chantarasriwong, Oraphin, Bashayer D. Althufairi, Nicholas J. Checchia, and Emmanuel A. Theodorakis. 2018. “Caged Garcinia Xanthones: Synthetic Studies and Pharmacophore Evaluation.” Pp. 93–131 in Studies in Natural Products Chemistry. Vol. 58. Elsevier B.V.Chaudhury, Arun, Chitharanjan Duvoor, Vijaya Dendi, Reddy Kraleti Sena, Aditya Chada Shashank, Rahul Ravilla, Asween Marco, Nawal Singh Shekhawat, Maria Theresa Montales, Kevin Kuriakose, Appalanaidu Sasapu, Alexandria Beebe, Naveen Patil, Chaitanya K. Musham Lohani, and Govinda Prasad Mirza. 2017. “Clinical Review of Antidiabetic Drugs: Implications for Type 2 Diabetes Mellitus Management.” Frontiers in Endocrinology 8(6):208–10.Che Hassan, Nurul Khairina Najwa, Muhammad Taher, and Deny Susanti. 2018. “Phytochemical Constituents and Pharmacological Properties of Garcinia Xanthochymus- a Review.” Biomedicine and Pharmacotherapy 106(April):1378–89.Chen, Lih Geeng, Ling Ling Yang, and Ching Chiung Wang. 2008. “Anti-Inflammatory Activity of Mangostins from Garcinia Mangostana.” Food and Chemical Toxicology 46(2):688–93.Chintoju, Navajyothi, Prasanthi Konduru, Rajya Lakshmi Kathula, and Ravalli Remella. 2015. “Importance of Natural Products in the Modern History.” Research & Reviews: Journal of Hospital and Clinical Pharmacy 1(1):5–10.Corbatón Anchuelo, A., R. Cuervo Pinto, and M. Serrano Ríos. 2004. “Diabetes Mellitus. Concepto, Clasificación y Mecanismos Etiopatogénicos.” Medicine - Programa de Formación Médica Continuada Acreditado 9(16):963–70.Costa Gil, José Esteban, and Eduardo Spinedi. 2017. “La Tormentosa Relación Entre Las Grasas y El Desarrollo de La Diabetes Mellitus de Tipo 2: Actualizado. Parte 1.” Revista Argentina de Endocrinología y Metabolismo 1–15.Cruz, Maria I. 2017. “Dual/Multitargeted Xanthone Derivatives for Alzheimer’s Disease: Where Do We Stand?” Future Medicinal Chemistry 9(14):1611–30.Deachathai, S., W. Mahabusarakam, S. Phongpaichit, and W. C. Taylor. 2005. “Phenolic Compounds from the Fruit of Garcinia Dulcis.” Phytochemistry 66(19):2368–75.Ernst, Heidi A., Leila Lo Leggio, Martin Willemoës, Gordon Leonard, Paul Blum, and Sine Larsen. 2006. “Structure of the Sulfolobus Solfataricus α-Glucosidase: Implications for Domain Conservation and Substrate Recognition in GH31.” Journal of Molecular Biology 358(4):1106–24.Farrington, Rachael, Ian F. Musgrave, and Roger W. Byard. 2019. “Evidence for the Efficacy and Safety of Herbal Weight Loss Preparations.” Journal of Integrative Medicine (December 2018).Fischer, André, Manuel Smiesko, Martin Sellner, and Markus A. Lill. 2020. “Decision Making in Structure-Based Drug Discovery: Visual Inspection of Docking Results ̌.” Journal of Medicinal Chemistry.Fundación para la Diabetes, and Novo Nordisk. 2020. “2004: Diabetes y Obesidad.” 14 de Noviembre, Día Mundial de LaDiabetes 2004 21(1):1–9. Retrieved (https://www.fundaciondiabetes.org/diamundial/353/2004-diabetes-y-obesidad).Gai-Li, Li, Cai Chao-Yun, He Jia-Yun, Li Rao, Lin Ma, Yan Liu, and Bo Wang. 2016. “Synthesis of 3-Acyloxyxanthone Derivatives as α-Glucosidase Inhibitors: A Further Insight into the 3-Substituents’ Effect.” Bioorganic and Medicinal Chemistry 24(7):1431–38.García Martín, Pilar, and Margarita Vega Holm. 2018. “Pilar García Martín Fármacos Multidiana. Aplicaciones Terapéuticas.” Gendaram, Odontuya, Lai Daowan, Purevdorj Erdenetsogt, and Proksch Peter. 2017. “Pancreatic Lipase Inhibitory and Antioxidative Constituents from the Aerial Parts of Paeonia Lactiflora Pall. (Ranunculaceae).” Phytochemistry Letters 21(2017):240–46.Genovese, Salvatore, Serena Fiorito, Vito Alessandro Taddeo, and Francesco Epifano. 2016. “Recent Developments in the Pharmacology of Prenylated Xanthones.” Drug Discovery Today 21(11):1814–19.Gokaraju, Ganga. 2009. “Wo 2009/093259 A2.” (12).Goodsell, David S., Garrett M. Morris, and Arthur J. Olson. 1996. “Automated Docking.” Journal of Molecular Recognition 9(November 1995):1–5.Gorgojo-Martínez, J. J. 2014. “Nuevos Fármacos Antidiabéticos: Avanzando Hacia El Control Integral de La Diabesidad.” Hipertension y Riesgo Vascular 31(2):45–57.Gu, Yeyi, William J. Hurst, David A. Stuart, and Joshua D. Lambert. 2011. “Inhibition of Key Digestive Enzymes by Cocoa Extracts and Procyanidins.” Journal of Agricultural and Food Chemistry 59(10):5305–11.Ha, Ly Dieu, Poul Erik Hansen, Ole Vang, Fritz Duus, Hung Dinh Pham, and Lien Hoa Dieu Nguyen. 2009. “Cytotoxic Geranylated Xanthones and O-Alkylated Derivatives of α-Mangostin.” Chemical and Pharmaceutical Bulletin 57(8):830–34.Han, Ah Reum, Jeong Ah Kim, Daniel D. Lantvit, Leonardus B. S. Kardono, Soedarsono Riswan, Heebyung Chai, Esperanza J. Carcach. De Blanco, Norman R. Farnsworth, Steven M. Swanson, and A. Douglas Kinghorn. 2009. “Cytotoxic Xanthone Constituents of the Stem Bark of Garcinia Mangostana (Mangosteen).” Journal of Natural Products 72(11):2028–31.Hasenah, Ali., P. J. Houghton, and A. Soumyanath. 2006. “α-Amylase Inhibitory Activity of Some Malaysian Plants Used to Treat Diabetes; with Particular Reference to Phyllanthus Amarus.” Journal of Ethnopharmacology 107(3):449–55.Hiếu, Nguyễn Trí, Hà Diệu Ly, Phạm Đình Hùng, and Nguyễn D. Liên Hoa. 2009. “Isolation and Structural Identification of Five Xanthone Derivatives from the Pericarps of Garcinia Mangostana L.” Tap Chi Duoc Hoc 48(8):18–22.Ibrahim, Sabrin R. M., Hossam M. Abdallah, Ali M. El-Halawany, Mohammed F. Radwan, Ibrahim A. Shehata, Essam M. Al-Harshany, Mohamed F. Zayed, and Gamal A. Mohamed. 2018. “Garcixanthones B and C, New Xanthones from the Pericarps of Garcinia Mangostana and Their Cytotoxic Activity.” Phytochemistry Letters 25(March):12–16.Ibrahim, Sabrin R. M., Gamal A. Mohamed, Maan T. Khayat, Sahar Ahmed, Hany Abo-Haded, and Khalid Z. Alshali. 2019. “Mangostanaxanthone VIIII, a New Xanthone from Garcinia Mangostana Pericarps, α-Amylase Inhibitory Activity, and Molecular Docking Studies.” Brazilian Journal of Pharmacognosy 29(2):206–12.Islas Andrade, Sergio A., and María Cristina Revilla Monsalve. 2013. Diabetes Mellitus: Actualizaciones. S.E. edited by S. A. de C. V. Editorial Alfil. México D. F.Ito, Chihiro, Masataka Itoigawa, Tomoko Takakura, Nijisiri Ruangrungsi, Fumio Enjo, Harukuni Tokuda, Hoyoku Nishino, and Hiroshi Furukawa. 2003. “Chemical Constituents of Garcinia Fusca: Structure Elucidation of Eight New Xanthones and Their Cancer Chemopreventive Activity.” Journal of Natural Products 66(2):200–205.Iwai, Kunihisa, Mi Yeon Kim, Akio Onodera, and Hajime Matsue. 2006. “α-Glucosidase Inhibitory and Antihyperglycemic Effects of Polyphenols in the Fruit of Viburnum Dilatatum Thunb.” Journal of Agricultural and Food Chemistry 54(13):4588–92.Ji, Xiuhong, Bharathi Avula, and Ikhlas A. Khan. 2007. “Quantitative and Qualitative Determination of Six Xanthones in Garcinia Mangostana L. by LC-PDA and LC-ESI-MS.” Journal of Pharmaceutical and Biomedical Analysis 43(4):1270–76.Jiang, He Zhong, Xiao Fang Quan, Wei Xi Tian, Jiang Miao Hu, Peng Cheng Wang, Sheng Zhuo Huang, Zhong Quan Cheng, Wen Juan Liang, Jun Zhou, Xiao Feng Ma, and You Xing Zhao. 2010. “Fatty Acid Synthase Inhibitors of Phenolic Constituents Isolated from Garcinia Mangostana.” Bioorganic and Medicinal Chemistry Letters 20(20):6045–47.Johnson, Philip J., Charles E. Wiedmeyer, Alison LaCarrubba, V. K. Ganjam, and Nat T. Messer IV. 2012. “Diabetes, Insulin Resistance,and Metabolic Syndrome in Horses.” Journal of Diabetes Science and Technology 6(3):534–40.Keilany, Ziad. 2005. “Natural Products. Drug Discovery and Therapeu- Tic Medicine.” Review of Social Economy 36(2):228–29.Khaw, K. Y., S. B. Choi, S. C. Tan, H. A. Wahab, K. L. Chan, and V. Murugaiyah. 2014. “Prenylated Xanthones from Mangosteen as Promising Cholinesterase Inhibitors and Their Molecular Docking Studies.” Phytomedicine 21(11):1303–9.Kim, Jang Hoon, Hyo Young Kim, Seo Young Yang, Jin Baek Kim, Chang Hyun Jin, and Young Ho Kim. 2018. “Inhibitory Activity of (−)-Epicatechin-3,5-O-Digallate on α-Glucosidase and in Silico Analysis.” International Journal of Biological Macromolecules 107(PartA):1162–67.Kulkarni, P. P., A. J. Kadam, R. B. Mane, Uday V. Desai, and P. P. Wadgaonkar. 1999. “Demethylation of Methyl Aryl Ethers Using Pyridine Hydrochloride in Solvent-Free Conditions under Microwave Irradiation.” Journal of Chemical Research 6(394–395):1–2.Lanchero Barrios, Irvyng Patrick. 2016. “Irvyng Patrick Lanchero Barrios.” Universidad Nacional de Colombia (Tesis de maestría).Le, My Phuong T., Miguel A. Lanaspa, Christina M. Cicerchi, Jatinder Rana, Jeffrey D. Scholten, Brandi L. Hunter, Christopher J. Rivard, R. Keith Randolph, and Richard J. Johnson. 2016. “Bioactivity-Guided Identification of Botanical Inhibitors of Ketohexokinase.” PLoS ONE 11(6):1–17.Lee, Young A., Eun Ju Cho, Takashi Tanaka, and Takako Yokozawa. 2007. “Inhibitory Activities of Proanthocyanidins from Persimmon against Oxidative Stress and Digestive Enzymes Related to Diabetes.” Journal of Nutritional Science and Vitaminology 53(3):287–92.Li, Huilin, Fengrui Song, Junpeng Xing, Rong Tsao, Zhiqiang Liu, and Shuying Liu. 2009. “Screening and Structural Characterization of α-Glucosidase Inhibitors from Hawthorn Leaf Flavonoids Extract by Ultrafiltration LC-DAD-MSnand SORI-CID FTICR MS.” Journal of the American Society for Mass Spectrometry 20(8):1496–1503.Li, Jin, Ailing Fu, and Le Zhang. 2019. “An Overview of Scoring Functions Used for Protein–Ligand Interactions in Molecular Docking.” Interdisciplinary Sciences: Computational Life Sciences 11(2):320–28.Li, Zuo Peng, Yeong Hun Song, Zia Uddin, Yan Wang, and Ki Hun Park. 2018. “Inhibition of Protein Tyrosine Phosphatase 1B (PTP1B) and α-Glucosidase by Xanthones from Cratoxylum Cochinchinense, and Their Kinetic Characterization.” Bioorganic and Medicinal Chemistry 26(3):737–46.Libert, Diane M., Amy S. Nowacki, and Marvin R. Natowicz. 2018. “Metabolomic Analysis of Obesity, Metabolic Syndrome, and Type 2 Diabetes: Amino Acid and Acylcarnitine Levels Change along a Spectrum of Metabolic Wellness.” PeerJ 2018(8).Lim, T. K. 2012. “Edible Medicinal and Non-Medicinal Plants: Volume 2, Fruits.” Edible Medicinal and Non-Medicinal Plants: Volume 2, Fruits 2:1–1088.Liu, Qianyu, Dan Li, Anqi Wang, Zhen Dong, Sheng Yin, Qingwen Zhang, Yang Ye, Liangchun Li, and Ligen Lin. 2016. “Nitric Oxide Inhibitory Xanthones from the Pericarps of Garcinia Mangostana.” Phytochemistry 131:115–23.López Vallejo, Fabián, José Luis Medina Franco, and Rafael Castillo. 2018. “Diseño de Fármacos Asistido Por Computadora.” Educación Química 17(4):452.Mahendran, G., M. Manoj, K. J. Rajendra Prasad, and V. Narmatha Bai. 2015. “Antioxidants, Anti-Proliferative, Anti-Inflammatory, Anti-Diabetic and Anti-Microbial Effects of Isolated Compounds from Swertia Corymbosa (Grieb.) Wight Ex C.B. Clark – An in Vitro Approach.” Food Science and Human Wellness 4(4):169–79.Marrelli, Mariangela, Monica Rosa Loizzo, Marcello Nicoletti, Francesco Menichini, and Filomena Conforti. 2013. “Inhibition of Key Enzymes Linked to Obesity by Preparations From Mediterranean Dietary Plants: Effects on α-Amylase and Pancreatic Lipase Activities.” Plant Foods for Human Nutrition 68(4):340–46.Martínez Grau, M. ángeles, and Aurelio G. Csákÿ. 2012. Técnicas Experimentales En Síntesis Orgánica. Segunda ed. edited by S. A. EDITORIAL SÍNTESIS.Medellín Zabala, Diana Marcela. 2016. “Sistemática Del Género Garcinia (Clusiaceae): Revisión Taxonómica Para Colombia y Filogenia de Las Especies Neotropicales.” Universidad Nacional de Colombia (Tesis de Maestría).Medina-Franco, José L., Eli Fernán-Dezde Gortari, and J. Jesús Naveja. 2015. “Avances En El Diseño de Fármacos Asistido Por Computadora.” Educacion Quimica 26(3):180–86.Mignani, Serge, Scot Huber, Helena Tomás, João Rodrigues, and Jean Pierre Majoral. 2016. “Why and How Have Drug Discovery Strategies in Pharma Changed? What Are the New Mindsets?” Drug Discovery Today 21(2):239–49.Mohamed Ibrahim, Sabrin Ragab, Gamal Abdallah Mohamed, Maan Talaat Abdullah Khayat, Sahar Ahmed, and Hany Abo-Haded. 2019. “α-Amylase Inhibition of Xanthones from Garcinia Mangostana Pericarps and Their Possible Use for the Treatment of Diabetes with Molecular Docking Studies.” Journal of Food Biochemistry 43(5):1–9.Morales Gómez, Angy Tatiana. 2017. “Determinación Del Potencial Inhibidor Del Extracto y Fracciones de Passiflora Manicata Sobre Enzimas Digestivas (α-Amilasa, α-Glucosidasa y Lipasa Pancreática).” Pontificia Universidad Javeriana (Tesis de Maestría).Morelli, Carlo F., Marco Biagiotti, Valeria M. Pappalardo, Marco Rabuffetti, and Giovanna Speranza. 2015. “Chemistry of α-Mangostin. Studies on the Semisynthesis of Minor Xanthones from Garcinia Mangostana.” Natural Product Research 29(8):750–55.Nagem, Tanus Jorge, and Fernando Faustino De Oliveira. 1997. “Xanthones and Other Constituents of Vismia Parviflora.” Journal of the Brazilian Chemical Society 8(5):505–8.Neves, Bruno J., Rodolpho C. Braga, Cleber C. Melo-Filho, José Teófilo Moreira-Filho, Eugene N. Muratov, and Carolina Horta Andrade. 2018. “QSAR-Based Virtual Screening: Advances and Applications in Drug Discovery.” Frontiers in Pharmacology 9(NOV).Newman, David J., and Gordon M. Cragg. 2020. “Natural Products as Sources of New Drugs over the Nearly Four Decades from 01/1981 to 09/2019.” Journal of Natural Products 83(3):770–803.Nguyen, Chi N., Binh T. D. Trinh, Toan B. Tran, Le Thu T. Nguyen, Anna K. Jäger, and Lien Hoa D. Nguyen. 2017. “Anti-Diabetic Xanthones from the Bark of Garcinia Xanthochymus.” Bioorganic and Medicinal Chemistry Letters 27(15):3301–4. Nisha, J. 2017. “In-Silico Screening of Alpha Amylase Enzyme Inhibitors from Siddha Formulation Pungampoo Chooranam by Molecular Docking Analysis for the Management of Type II Diabetes Mellitus.” International Journal of Current Research in Medical Sciences 3(10):24–34.Ochir, Sarangowa, Makoto Nishizawa, Byoung Jae Park, Kouta Ishii, Tsutomu Kanazawa, Minoru Funaki, and Takashi Yamagishi. 2010. “Inhibitory Effects of Rosa Gallica on the Digestive Enzymes.” Journal of Natural Medicines 64(3):275–80. Oda, Akifumi, Keiichi Tsuchida, Tadakazu Takakura, Noriyuki Yamaotsu, and Shuichi Hirono. 2006. “Comparison of Consensus Scoring Strategies for Evaluating Computational Models of Protein - Ligand Complexes.” 380–91.OMS/OPS. 2017. “La Obesidad Entre Los Niños y Los Adolescentes Se Ha Multiplicado Por 10 En Los Cuatro Últimos Decenios.” Protección & Seguridad En La Comunidad 1–6. Retrieved (http://www.who.int/mediacentre/news/releases/2017/increase-childhood-obesity/es/).OMS. 2013. Estrategia de Medicina Tradicional de La OMS 2014-2023. 1 edición. edited by Organización mundial de la salud and W. Chokwiwat.OMS. 2018. “Obesidad y Sobrepeso.” Obesidad y Sobrepeso. Retrieved (http://www.who.int/es/news-room/fact-sheets/detail/obesity-and-overweight).OPS/OMS Colombia. 2018. “OPS- Enfermedades No Transmitibles.Pdf.”Palacio-Rodríguez, Karen, Isaias Lans, Claudio N. Cavasotto, and Pilar Cossio. 2019. “Exponential Consensus Ranking Improves the Outcome in Docking and Receptor Ensemble Docking.” Scientific Reports 9(1):1–14. Pappachan, Joseph M., Cornelius J. Fernandez, and Elias C. Chacko. 2019. “Diabesity and Antidiabetic Drugs.” Molecular Aspects of Medicine 66(August):3–12.Pedraza-Chaverri, José, Noemí Cárdenas-Rodríguez, Marisol Orozco-Ibarra, and Jazmin M. Pérez-Rojas. 2008. “Medicinal Properties of Mangosteen (Garcinia Mangostana).” Food and Chemical Toxicology 46(10):3227–39.Peres, Valdir, Tanus Jorge Nagem, and Fernando Faustino De Oliveira. 2000. “Tetraoxygenated Naturally Occurring Xanthones.” Phytochemistry 55(7):683–710.Pérez-Sánchez, H., G. Cano, J. García-Rodríguez, and J. M. Cecilia. 2015. “Descubrimiento de Fármacos Basado En Cribado Virtual Refinado Con Enfoques Neuronales Paralelos.” Revista Internacional de Metodos Numericos Para Calculo y Diseno En Ingenieria 31(4):207–11.Pierre Egloff, Marie, Frank Marguet, Gerard Buono, Robert Venger, Christian* Camillau, and Herman Von Tilbeurgho. 1995. “A Resolution Structure of the Pancreatic Lipase-Colipase Complex.” Biochemistry 34:2751–62.Pleiss, Jürgen, Markus Fischer, Marcus Peiker, Claudia Thiele, and Rolf D. Schmid. 2000. “Lipase Engineering Database.” Journal of Molecular Catalysis B: Enzymatic 10(5):491–508.Ponce, Jorge Orlando, Nazarena Rodriguez Vigay, and rolando pablo Juarez. 2019. “Inhibición α -Amilasa Por Medio de Extractos de Plantas Medicinales Como Tratamiento Complementario/Alternativo de La Diabetes y La Caries.” Revista de La Sociedad Odontolólgica de La Plata (SOLP) 55(May 2018):41–44.Preto, Jordane, and Francesco Gentile. 2019. “Assessing and Improving the Performance of Consensus Docking Strategies Using the DockBox Package.” Journal of Computer-Aided Molecular Design 33(9):817–29.Qian, Minxie, Silvia Spinelli, Hugues Driguez, and Françoise Payan. 1997. “Structure of a Pancreatic α-Amylase Bound to a Substrate Analogue at 2.03 Å Resolution.” Protein Science 6(11):2285–96.Raksat, Achara, Piyaporn Phukhatmuen, Jianxiong Yang, Wisanu Maneerat, Rawiwan Charoensup, Raymond J. Andersen, Yan A. Wang, Stephen G. Pyne, and Surat Laphookhieo. 2020. “Phloroglucinol Benzophenones and Xanthones from the Leaves of Garcinia Cowa and Their Nitric Oxide Production and α-Glucosidase Inhibitory Activities.” Journal of Natural Products 83(1):164–68.Raksat, Achara, Tawanun Sripisut, and Wisanu Maneerat. 2015. “Bioactive Xanthones from Cratoxylum Cochinchinense.” Natural Product Communications 10(11):1969–72.Rao, P. Suryaprakasa, P. Prabhakara Reddy, and T. R. Seshadri. 1940. “Methylation of Hydroxy Flavonols Using Methyl Iodide and Potassium Carbonate.” Proceedings of the Indian Academy of Sciences - Section A 12(6):495–97.Ren, Yulin, Susan Matthew, Daniel D. Lantvit, Tran Ngoc Ninh, Heebyung Chai, James R. Fuchs, Djaja D. Soejarto, Esperanza J. Carcach. De Blanco, Steven M. Swanson, and A. Douglas Kinghorn. 2011. “Cytotoxic and NF-ΚB Inhibitory Constituents of the Stems of Cratoxylum Cochinchinense and Their Semisynthetic Analogues.” Journal of Natural Products 74(5):1117–25.Repasky, Matthew P., Mee Shelley, and Richard A. Friesner. 2007. “Flexible Ligand Docking with Glide.” Pp. 1–36 in Current Protocols in Bioinformatics.Rodriguez, E., J. M. Perea, A. M. Ortega, and R. M. López-sobaler. 2009. “Obesidad, Resistencia a La Insulina y Aumento de Los Niveles de Adipoquinas: Importancia de La Dieta y El Ejercicio Físico.” Nutrición Hospitalaria 24(4):415–21.Ryu, Hyung Won, Jung Keun Cho, Marcus J. Curtis-Long, Heung Joo Yuk, Young Soo Kim, Sunin Jung, Young Suk Kim, ByongWon Lee, and Ki Hun Park. 2011. “α-Glucosidase Inhibition and Antihyperglycemic Activity of Prenylated Xanthones from Garcinia Mangostana.” Phytochemistry 72(17):2148–54.Saboury, A. A. 2009. “Enzyme Inhibition and Activation: A General Theory.” Journal of the Iranian Chemical Society 6(2):219–29.Salud, Ministerio de. 2005. Guía de Atención de La Obesidad. Bogotá D. C.Salvador Rodríguez, J., C. Abreu Padín, F. Rotellar Sastre, and G. Frühbeck Martínez. 2004. “Tratamiento de La Obesidad. Medidas de Estilo de Vida y Régimen Alimentario. Tratamiento Farmacológico. Tratamiento Quirúrgico.” Medicine - Programa de Formación Médica Continuada Acreditado 9(19):1176–85.Sankar, Veintramuthu, and S. .. Maida Engels. 2018. “Synthesis, Biological Evaluation, Molecular Docking and in Silico ADME Studies of Phenacyl Esters of N-Phthaloyl Amino Acids as Pancreatic Lipase Inhibitors.” Future Journal of Pharmaceutical Sciences 4(2):276–83.Santos, Clementina M. M., Marisa Freitas, and Eduarda Fernandes. 2018. “A Comprehensive Review on Xanthone Derivatives as α-Glucosidase Inhibitors.” European Journal of Medicinal Chemistry 157:1460–79.Sassaki, Guilherme L., Marcello Iacomini, and Philip A. J. Gorin. 2005. “Methylation-GC-MS Analysis of Arabinofuranose- And Galactofuranose- Containing Structures: Rapid Synthesis of Partially O-Methylated Alditol Acetate Standards.” Anais Da Academia Brasileira de Ciencias 77(2):223–34.Sekhon-Loodu, Satvir, and H. P. Vasanth. Rupasinghe. 2019. “Evaluation of Antioxidant, Antidiabetic and Antiobesity Potential of Selected Traditional Medicinal Plants.” Frontiers in Nutrition 6.Shakoor, Hira, Fatima Abdelfattah, Khaula Albadi, Mentalla Adib, Jaleel Kizhakkayil, and Carine Platat. 2020. “Inhibition of Digestive Enzyme and Stimulation of Human Liver Cells (HepG2) Glucose Uptake by Date Seeds Extract.” Evidence-Based Complementary and Alternative Medicine 2020.Shang, Erchang, Yaxia Yuan, Xinyi Chen, Ying Liu, Jianfeng Pei, and Luhua Lai. 2014. “De Novo Design of Multitarget Ligands with an Iterative Fragment-Growing Strategy.” Journal of Chemical Information and Modeling 54(4):1235–41.Da Silva, Franck, Jeremy Desaphy, and Didier Rognan. 2018. “IChem: A Versatile Toolkit for Detecting, Comparing, and Predicting Protein–Ligand Interactions.” ChemMedChem 13(6):507–10.Sim, Lyann, Roberto Quezada-Calvillo, Erwin E. Sterchi, Buford L. Nichols, and David R. Rose. 2008. “Human Intestinal Maltase-Glucoamylase: Crystal Structure of the N-Terminal Catalytic Subunit and Basis of Inhibition and Substrate Specificity.” Journal of Molecular Biology 375(3):782–92.Sriyatep, Teerayut, Ittipon Siridechakorn, Wisanu Maneerat, Acharavadee Pansanit, Thunwadee Ritthiwigrom, Raymond J. Andersen, and Surat Laphookhieo. 2015. “Bioactive Prenylated Xanthones from the Young Fruits and Flowers of Garcinia Cowa.” Journal of Natural Products 78(2):265–71.Sriyatep, Teerayut, Cholpisut Tantapakul, Raymond J. Andersen, Brian O. Patrick, Stephen G. Pyne, Chatchai Muanprasat, Sawinee Seemakhan, Suparerk Borwornpinyo, and Surat Laphookhieo. 2018. “Resolution and Identification of Scalemic Caged Xanthones from the Leaf Extract of Garcinia Propinqua Having Potent Cytotoxicities against Colon Cancer Cells.” Fitoterapia 124(October):34–41.Sudta, Pichit, Payung Jiarawapi, Apichart Suksamrarn, Poonpilas Hongmanee, and Sunit Suksamrarn. 2013. “Potent Activity against Multidrug-Resistant Mycobacterium Tuberculosis of α-Mangostin Analogs.” Chemical and Pharmaceutical Bulletin 61(2):194–203.Sukandar, Edwin Risky, Sutin Kaennakam, Kitiya Rassamee, Taslim Ersam, Pongpun Siripong, and Santi Tip-Pyang. 2019. “Tetrandraxanthones A-I, Prenylated and Geranylated Xanthones from the Stem Bark of Garcinia Tetrandra.” Journal of Natural Products 82(5):1312–18.Sukandar, Edwin Risky, Sutin Kaennakam, Kitiya Rassamee, Pongpun Siripong, Sri Fatmawati, Taslim Ersam, and Santi Tip-pyang. 2018. “Xanthones and Biphenyls from the Stems of Garcinia Cylindrocarpa and Their Cytotoxicity.” Fitoterapia 130(August):112–17.Sultanbawa, M. U. S. 1980. “Xanthonoids of Tropical Plants.” Tetrahedron 36(11):1465–1506.Sumaryada, T., and A. W. Roslia. 2016. “Molecular Docking Simulation of Mangostin Derivatives and Curcuminoid on Maltase- Glucoamylase Target for Searching Anti-Diabetes Drug Candidates.” 1st International Conference on Biomedical Engineering (IBIOMED, 1–4.Taha, Muhammad, Nor Hadiani Ismail, Kulsoom Javaid, Syahrul Imran, El Hassane Anouar, Abdul Wadood, Atia-Tul-Wahab, Muhammad Ali, Khalid Mohammed Khan, Syed Muhammad Saad, Fazal Rahim, and M. Iqbal Choudhary. 2015. “Evaluation of 2-Indolcarbohydrazones as Potent α-Glucosidase Inhibitors, in Silico Studies and DFT Based Stereochemical Predictions.” Bioorganic Chemistry 63:24–35.Torres R, Eugenio, Manuel Almeida S, and Christian Vogel. 2015. “Síntesis y Evaluación de La Actividad Antitumoral in Vitro de Un Éster Prenilado Análogo a Productos Naturales.” Química Viva 14(1):111–19.Trott, Oleg, and Arthur J. Olson. 2012. “Software News and Update AutoDock Vina: Improving the Speed and Accuracy of Docking with a New Scoring Function, Efficient Optimization, and Multithreading.” Journal of Computational Chemistry 32:174–82.Tusevski, Oliver, Branka Vinterhalter, Dijana Krstić Milošević, Marina Soković, Ana Ćirić, Dragan Vinterhalter, Snežana Zdravković Korać, Jasmina Petreska Stanoeva, Marina Stefova, and Sonja Gadzovska Simic. 2017. “Production of Phenolic Compounds, Antioxidant and Antimicrobial Activities in Hairy Root and Shoot Cultures of Hypericum Perforatum L.” Plant Cell, Tissue and Organ Culture 128(3):589–605.Ubukata, Makoto, Hitomi Takamori, Misaki Ohashi, Shinya Mitsuhashi, Kaoru Yamashita, Tomohisa Asada, Noriyuki Nakajima, Nobuyasu Matsuura, Mie Tsuruga, Keiko Taki, and Junji Magae. 2007. “Mycophenolic Acid as a Latent Agonist of PPARγ.” Bioorganic and Medicinal Chemistry Letters 17(17):4767–70.Uthuppan, Jasmine, and K. Soni. 2013. “Conformational Analysis: A Review.” International Journal of Pharmaceutical Sciences & … 4(1):34–41.Veeramachaneni, Ganesh Kumar, K. Kranthi Raj, Leela Madhuri Chalasani, Sai Krishna Annamraju, JS Bondili, and Venkateswara Talluri. 2015. “Shape Based Virtual Screening and Molecular Docking towards Designing Novel Pancreatic Lipase Inhibitors.” Bioinformation 11(12):535–42.Villarroya, Francesc. 2016. “Bioquimica De La Obesidad.” Sociedad Española de Bioquímica y Biología Molecular 190:28.Vongsak, Boonyadist, Sumet Kongkiatpaiboon, Sunan Jaisamut, Sasipawan Machana, and Chamnan Pattarapanich. 2015. “In Vitro Alpha Glucosidase Inhibition and Free-Radical Scavenging Activity of Propolis from Thai Stingless Bees in Mangosteen Orchard.” Brazilian Journal of Pharmacognosy 25(5):445–50.Walker, Edward B. 2007. “HPLC Analysis of Selected Xanthones in Mangosteen Fruit.” Journal of Separation Science 30(9):1229–34.Wang, Jing J., Qing H. Shi, Wei Zhang, and Barbara J. S. Sanderson. 2012. “Anti-Skin Cancer Properties of Phenolic-Rich Extract from the Pericarp of Mangosteen (Garcinia Mangostana Linn.).” Food and Chemical Toxicology 50(9):3004–13.Wang, Ming Hui, Kuo Jun ZHANG, Qin Lan GU, Xiao Ling BI, and Jin Xin WANG. 2017. “Pharmacology of Mangostins and Their Derivatives: A Comprehensive Review.” Chinese Journal of Natural Medicines 15(2):81–93.Wang, Zerong. 2010. “Irvine-Purdie Methylation.” Comprehensive Organic Name Reactions and Reagents 1526–29.Whitcomb, David C., and Mark E. Lowe. 2007. “Human Pancreatic Digestive Enzymes.” Digestive Diseases and Sciences 52(1):1–17.Williams, John A. 2017. “Amylase.” Pancreapedia 1.Williams, L. K., C. Li, S. G. Withers, and G. D. Brayer. 2012. “Order and Disorder: Differential Structural Impacts of Myricetin and Ethyl Caffeate on Human Amylase, an Antidiabetic Target.” J.Med.Chem. 55(101):77–86.Xu, Youjun, Shiwei Wang, Qiwan Hu, Shuaishi Gao, Xiaomin Ma, Weilin Zhang, Yihang Shen, Fangjin Chen, Luhua Lai, and Jianfeng Pei. 2018. “CavityPlus: A Web Server for Protein Cavity Detection with Pharmacophore Modelling, Allosteric Site Identification and Covalent Ligand Binding Ability Prediction.” Nucleic Acids Research 46(W1):W374–79.Yang, Hye Won, K. H. N. Fernando, Jae Young Oh, Xining Li, You Jin Jeon, and Bo Mi Ryu. 2019. “Anti-Obesity and Anti-Diabetic Effects of Ishige Okamurae.” Marine Drugs 17(4):1–11.Ye, Gao Jie, Tian Lan, Zhi Xin Huang, Xiao Ning Cheng, Chao Yun Cai, Sen Miao Ding, Min Li Xie, and Bo Wang. 2019. “Design and Synthesis of Novel Xanthone-Triazole Derivatives as Potential Antidiabetic Agents: α-Glucosidase Inhibition and Glucose Uptake Promotion.” European Journal of Medicinal Chemistry 177:362–73.Yeong, Keng Yoon, Kooi Yeong Khaw, Yukari Takahashi, Yukihiro Itoh, Vikneswaran Murugaiyah, and Takayoshi Suzuki. 2020. “Discovery of Gamma-Mangostin from Garcinia Mangostana as a Potent and Selective Natural SIRT2 Inhibitor.” Bioorganic Chemistry 94(June):103403.Yuan, Haidan, Qianqian Ma, Li Ye, and Guangchun Piao. 2016. “The Traditional Medicine and Modern Medicine from Natural Products.” Molecules 21(5).Zawawi, Nik Khairunissa Nik Abdullah, Muhammad Taha, Norizan Ahmat, Abdul Wadood, Nor Hadiani Ismail, Fazal Rahim, Syed Sikander Azam, and Noraishah Abdullah. 2016. “Benzimidazole Derivatives as New α-Glucosidase Inhibitors and in Silico Studies.” Bioorganic Chemistry 64:29–36.Zhang, Bao Jun, Wen Wei Fu, Rong Wu, Jin Ling Yang, Cai Yun Yao, Bing Xiong Yan, Hong Sheng Tan, Chang Wu Zheng, Zhi Jun Song, and Hong Xi Xu. 2019. “Cytotoxic Prenylated Xanthones from the Leaves of Garcinia Bracteata.” Planta Medica 85(6):444–52.Zhang, Weilin, Jianfeng Pei, and Luhua Lai. 2017. “Computational Multitarget Drug Design.” Journal of Chemical Information and Modeling 57(3):403–12.Zhang, Yaozheng, Zhijun Song, Jing Hao, Shengxiang Qiu, and Zhifang Xu. 2010. “Two New Prenylated Xanthones and a New Prenylated Tetrahydroxanthone from the Pericarp of Garcinia Mangostana.” Fitoterapia 81(6):595–99.Zheng, Guo qiang, Patrick M. Kenney, and Luke K. T. Lam. 1992. “Myristicin: A Potential Cancer Chemopreventive Agent from Parsley Leaf Oil.” Journal of Agricultural and Food Chemistry 40(1):107–10.Zheng, Huan Huan, Cui Ting Luo, Heru Chen, Juan Na Lin, Chun Ling Ye, Shuang Shuang Mao, and Yu Lin Li. 2014. “Xanthones from Swertia Mussotii as Multitarget-Directed Antidiabetic Agents.” ChemMedChem 9(7):1374–77.EspecializadaIdentificación de moléculas líderes de origen natural con acción polifarmacológica aplicables en el tratamiento de obesidad y diabetes tipo IIMinisterio de Ciencia, Tecnología e Innovación (MinCiencias)CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8805https://repositorio.unal.edu.co/bitstream/unal/79963/3/license_rdf4460e5956bc1d1639be9ae6146a50347MD53ORIGINAL1016077448.2021.pdf1016077448.2021.pdfTesis de Maestría en Ciencias - 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