Synthesis and cytotoxic activity of per-acetylated and halogenated derivatives of nucleosides in breast cancer cells
ABSTRACT: Objectives. To make the synthesis of halogenated derivatives on the nitrogenous base and their respective acyl ester and amide type derivatives for all hydroxyl and amine groups of the uridine and cytarabine nucleosides, and evaluate cytotoxicity against breast cancer cell line. Methods. F...
- Autores:
-
Berrío Escobar, Jhon Fernando
Pastrana Restrepo, Manuel Humberto
Galeano Jaramillo, Elkin de Jesús
Márquez Fernández, Diana Margarita
Márquez Fernández, María Elena
Martínez Martínez, Alejandro
- Tipo de recurso:
- Article of investigation
- Fecha de publicación:
- 2017
- Institución:
- Universidad de Antioquia
- Repositorio:
- Repositorio UdeA
- Idioma:
- eng
- OAI Identifier:
- oai:bibliotecadigital.udea.edu.co:10495/24051
- Acceso en línea:
- http://hdl.handle.net/10495/24051
http://revistaseug.ugr.es/index.php/ars/article/view/6441
- Palabra clave:
- Neoplasias de la Mama
Breast Neoplasms
Nucleósidos
Nucleosides
Uridina
Uridine
Citarabina
Cytarabine
Citotoxicidad
Cytotoxicity
http://aims.fao.org/aos/agrovoc/c_34251
- Rights
- openAccess
- License
- http://creativecommons.org/licenses/by-nc-sa/2.5/co/
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|
dc.title.spa.fl_str_mv |
Synthesis and cytotoxic activity of per-acetylated and halogenated derivatives of nucleosides in breast cancer cells |
dc.title.alternative.spa.fl_str_mv |
Síntesis y evaluación citotóxica de derivados halogenados y peracetylados de nucleósidos en células de cáncer de mama |
title |
Synthesis and cytotoxic activity of per-acetylated and halogenated derivatives of nucleosides in breast cancer cells |
spellingShingle |
Synthesis and cytotoxic activity of per-acetylated and halogenated derivatives of nucleosides in breast cancer cells Neoplasias de la Mama Breast Neoplasms Nucleósidos Nucleosides Uridina Uridine Citarabina Cytarabine Citotoxicidad Cytotoxicity http://aims.fao.org/aos/agrovoc/c_34251 |
title_short |
Synthesis and cytotoxic activity of per-acetylated and halogenated derivatives of nucleosides in breast cancer cells |
title_full |
Synthesis and cytotoxic activity of per-acetylated and halogenated derivatives of nucleosides in breast cancer cells |
title_fullStr |
Synthesis and cytotoxic activity of per-acetylated and halogenated derivatives of nucleosides in breast cancer cells |
title_full_unstemmed |
Synthesis and cytotoxic activity of per-acetylated and halogenated derivatives of nucleosides in breast cancer cells |
title_sort |
Synthesis and cytotoxic activity of per-acetylated and halogenated derivatives of nucleosides in breast cancer cells |
dc.creator.fl_str_mv |
Berrío Escobar, Jhon Fernando Pastrana Restrepo, Manuel Humberto Galeano Jaramillo, Elkin de Jesús Márquez Fernández, Diana Margarita Márquez Fernández, María Elena Martínez Martínez, Alejandro |
dc.contributor.author.none.fl_str_mv |
Berrío Escobar, Jhon Fernando Pastrana Restrepo, Manuel Humberto Galeano Jaramillo, Elkin de Jesús Márquez Fernández, Diana Margarita Márquez Fernández, María Elena Martínez Martínez, Alejandro |
dc.subject.decs.none.fl_str_mv |
Neoplasias de la Mama Breast Neoplasms Nucleósidos Nucleosides Uridina Uridine Citarabina Cytarabine |
topic |
Neoplasias de la Mama Breast Neoplasms Nucleósidos Nucleosides Uridina Uridine Citarabina Cytarabine Citotoxicidad Cytotoxicity http://aims.fao.org/aos/agrovoc/c_34251 |
dc.subject.agrovoc.none.fl_str_mv |
Citotoxicidad Cytotoxicity |
dc.subject.agrovocuri.none.fl_str_mv |
http://aims.fao.org/aos/agrovoc/c_34251 |
description |
ABSTRACT: Objectives. To make the synthesis of halogenated derivatives on the nitrogenous base and their respective acyl ester and amide type derivatives for all hydroxyl and amine groups of the uridine and cytarabine nucleosides, and evaluate cytotoxicity against breast cancer cell line. Methods. First, it was accomplished the halogenation reaction on the 5-position of the nitrogenous base, subsequently, the ester and amide derivatives were performed for all hydroxyl and amine group present in the nucleosides. Besides, the uridine acetonide derivatives as prepared by acid catalysis. The prod ucts were characterized by nuclear magnetic resonance spectroscopy (1H RMN y 13C RMN) and mass spectrometry in positive mode by direct injection. Derivatives were evaluated in Chinese hamster ovary (CHO-K1) and human breast cancer (MCF-7) cell lines. Results. The four derivatives were obtained with chlorine and bromine for the uridine and cytarabine, respectively, their respective per-acetylated derivatives, the per-acetylated nucleoside and the uridine acetonide; the compounds were obtained with efficiency over 90%. The per-acetylated nucleosides and the halogenated and per-acetylated derivatives did not show inhibitory effects on cell viability in MCF-7 cell line. However, the per-acetylated and halo genated derivatives presented a higher cytotoxic activity than their respective per-acetylated nucleoside. The uridine 3’,4’-acetonide showed a significant cytotoxicity on both cell lines.Conclusions. The per-acetylated nucleoside, and the respective halogenated derivatives with chlorine and bromine were obtained with high yields, nevertheless, these compounds did not exhibit a significant anti-proliferative activity (p˂0.05), possibly due to a low intra-cellular activation. |
publishDate |
2017 |
dc.date.issued.none.fl_str_mv |
2017 |
dc.date.accessioned.none.fl_str_mv |
2021-11-13T00:04:08Z |
dc.date.available.none.fl_str_mv |
2021-11-13T00:04:08Z |
dc.type.spa.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.coarversion.fl_str_mv |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
dc.type.hasversion.spa.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.coar.spa.fl_str_mv |
http://purl.org/coar/resource_type/c_2df8fbb1 |
dc.type.redcol.spa.fl_str_mv |
https://purl.org/redcol/resource_type/ART |
dc.type.local.spa.fl_str_mv |
Artículo de investigación |
format |
http://purl.org/coar/resource_type/c_2df8fbb1 |
status_str |
publishedVersion |
dc.identifier.issn.none.fl_str_mv |
0004-2927 2340-9894 |
dc.identifier.uri.none.fl_str_mv |
http://hdl.handle.net/10495/24051 |
dc.identifier.doi.none.fl_str_mv |
10.4321/S2340-98942017000400001 |
dc.identifier.url.spa.fl_str_mv |
http://revistaseug.ugr.es/index.php/ars/article/view/6441 |
identifier_str_mv |
0004-2927 2340-9894 10.4321/S2340-98942017000400001 |
url |
http://hdl.handle.net/10495/24051 http://revistaseug.ugr.es/index.php/ars/article/view/6441 |
dc.language.iso.spa.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartofjournalabbrev.spa.fl_str_mv |
Ars Pharm. |
dc.rights.spa.fl_str_mv |
info:eu-repo/semantics/openAccess |
dc.rights.uri.*.fl_str_mv |
http://creativecommons.org/licenses/by-nc-sa/2.5/co/ |
dc.rights.accessrights.spa.fl_str_mv |
http://purl.org/coar/access_right/c_abf2 |
dc.rights.creativecommons.spa.fl_str_mv |
https://creativecommons.org/licenses/by-nc-sa/4.0/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
http://creativecommons.org/licenses/by-nc-sa/2.5/co/ http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by-nc-sa/4.0/ |
dc.format.extent.spa.fl_str_mv |
10 |
dc.format.mimetype.spa.fl_str_mv |
application/pdf |
dc.publisher.spa.fl_str_mv |
Universidad de Granada, Facultad de Farmacia |
dc.publisher.group.spa.fl_str_mv |
Productos Naturales Marinos |
dc.publisher.place.spa.fl_str_mv |
Granada, España |
institution |
Universidad de Antioquia |
bitstream.url.fl_str_mv |
http://bibliotecadigital.udea.edu.co/bitstream/10495/24051/2/license_rdf http://bibliotecadigital.udea.edu.co/bitstream/10495/24051/3/license.txt http://bibliotecadigital.udea.edu.co/bitstream/10495/24051/1/BerrioJhon_2017_SynthesisCytotoxicActivityPer-acetylatedHalogenated.pdf |
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Repositorio Institucional Universidad de Antioquia |
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andres.perez@udea.edu.co |
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1812173225946251264 |
spelling |
Berrío Escobar, Jhon FernandoPastrana Restrepo, Manuel HumbertoGaleano Jaramillo, Elkin de JesúsMárquez Fernández, Diana MargaritaMárquez Fernández, María ElenaMartínez Martínez, Alejandro2021-11-13T00:04:08Z2021-11-13T00:04:08Z20170004-29272340-9894http://hdl.handle.net/10495/2405110.4321/S2340-98942017000400001http://revistaseug.ugr.es/index.php/ars/article/view/6441ABSTRACT: Objectives. To make the synthesis of halogenated derivatives on the nitrogenous base and their respective acyl ester and amide type derivatives for all hydroxyl and amine groups of the uridine and cytarabine nucleosides, and evaluate cytotoxicity against breast cancer cell line. Methods. First, it was accomplished the halogenation reaction on the 5-position of the nitrogenous base, subsequently, the ester and amide derivatives were performed for all hydroxyl and amine group present in the nucleosides. Besides, the uridine acetonide derivatives as prepared by acid catalysis. The prod ucts were characterized by nuclear magnetic resonance spectroscopy (1H RMN y 13C RMN) and mass spectrometry in positive mode by direct injection. Derivatives were evaluated in Chinese hamster ovary (CHO-K1) and human breast cancer (MCF-7) cell lines. Results. The four derivatives were obtained with chlorine and bromine for the uridine and cytarabine, respectively, their respective per-acetylated derivatives, the per-acetylated nucleoside and the uridine acetonide; the compounds were obtained with efficiency over 90%. The per-acetylated nucleosides and the halogenated and per-acetylated derivatives did not show inhibitory effects on cell viability in MCF-7 cell line. However, the per-acetylated and halo genated derivatives presented a higher cytotoxic activity than their respective per-acetylated nucleoside. The uridine 3’,4’-acetonide showed a significant cytotoxicity on both cell lines.Conclusions. The per-acetylated nucleoside, and the respective halogenated derivatives with chlorine and bromine were obtained with high yields, nevertheless, these compounds did not exhibit a significant anti-proliferative activity (p˂0.05), possibly due to a low intra-cellular activation.RESUMEN: Objetivos: Sintetizar derivados halogenados sobre la base nitrogenada, sus respectivos derivados tipo éster o amida de todos los grupos hidroxilo y amina presentes en los nucleósidos uridina y citarabina, y evaluar su actividad citotóxica sobre una línea celular de cáncer de mama. Metodología: primero se realizó la reacción de halogenación en la posición 5 de la base nitrogenada, posteriormente se formaron los ésteres y amidas de todos los grupos hidroxilos y amino presentes en los nucleósidos. Además, se preparó el derivado acetónido con catálisis ácida. Los compuestos se caracterizaron por espectroscopía de resonancia magnética nuclear (RMN 1H y RMN 13C) y espectrometría de masas por inyección directa en modo positivo. Los derivados se evaluaron sobre líneas celulares de tumor de Ovario de Hámster Chino (CHO) y de cáncer de mamá (MCF-7). Resultados: Se obtuvieron 4 derivados mono-halogenados con cloro y bromo de la uridina y citarabina, respectivamente, sus respectivos derivados per-acetilados, los nucleósidos per-acetilados y el acetónido de la uridina; los compuestos se obtuvieron con rendimientos superiores a 90%. Los nucleósidos peracetilados, y los derivados per-acetilados y halogenados no exhibieron una inhibición significativa de la viabilidad celular en ambas líneas celulares, sin embargo, de estos, los derivados per-acetilados y halogenados presentaron mayor actividad citotóxica que los respectivos nucleósidos per-acetilados. El derivado acetónido de la uridina mostró citotoxicidad significativa sobre ambas líneas celulares. Conclusiones: se obtuvieron los nucleósidos per-acetilados y los respectivos derivados clorados y bromados de estos, con rendimientos altos, sin embargo, estos compuestos no exhibieron una actividad anti-proliferativa significativa (p˂0,05), posiblemente debido a una baja activación intra-celular de los nucleósidos.COL001504310application/pdfengUniversidad de Granada, Facultad de FarmaciaProductos Naturales MarinosGranada, Españainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_2df8fbb1https://purl.org/redcol/resource_type/ARTArtículo de investigaciónhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/2.5/co/http://purl.org/coar/access_right/c_abf2https://creativecommons.org/licenses/by-nc-sa/4.0/Synthesis and cytotoxic activity of per-acetylated and halogenated derivatives of nucleosides in breast cancer cellsSíntesis y evaluación citotóxica de derivados halogenados y peracetylados de nucleósidos en células de cáncer de mamaNeoplasias de la MamaBreast NeoplasmsNucleósidosNucleosidesUridinaUridineCitarabinaCytarabineCitotoxicidadCytotoxicityhttp://aims.fao.org/aos/agrovoc/c_34251Ars Pharm.Ars Pharmaceutica145154584CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-81051http://bibliotecadigital.udea.edu.co/bitstream/10495/24051/2/license_rdfe2060682c9c70d4d30c83c51448f4eedMD52LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://bibliotecadigital.udea.edu.co/bitstream/10495/24051/3/license.txt8a4605be74aa9ea9d79846c1fba20a33MD53ORIGINALBerrioJhon_2017_SynthesisCytotoxicActivityPer-acetylatedHalogenated.pdfBerrioJhon_2017_SynthesisCytotoxicActivityPer-acetylatedHalogenated.pdfArtículo de investigaciónapplication/pdf650592http://bibliotecadigital.udea.edu.co/bitstream/10495/24051/1/BerrioJhon_2017_SynthesisCytotoxicActivityPer-acetylatedHalogenated.pdf7d60df163dd1bf4df1ba490a33e7327bMD5110495/24051oai:bibliotecadigital.udea.edu.co:10495/240512021-11-12 19:23:58.006Repositorio Institucional Universidad de Antioquiaandres.perez@udea.edu.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 |