Búsqueda de compuestos con posible actividad insecticida a partir de cianobacterias del Caribe colombiano

Se estudiaron tres mats de cianobacterias usando fraccionamiento bioguiado con el ensayo larvicida contra Aedes aegypti. Como compuestos activos se aislaron ácidos grasos insaturados, dos nuevos análogos de dolastatina D y el ácido seco malyngólido (nuevo), también la neodysidenina que afectó el des...

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Autores:: Ayala Muñoz, Farja Isabel

Tipo de recurso:

Fecha de publicación:: 2017

Institución:: Universidad Nacional de Colombia

Repositorio:: Universidad Nacional de Colombia

Idioma:: spa

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dc.title.spa.fl_str_mv	Búsqueda de compuestos con posible actividad insecticida a partir de cianobacterias del Caribe colombiano
title	Búsqueda de compuestos con posible actividad insecticida a partir de cianobacterias del Caribe colombiano
spellingShingle	Búsqueda de compuestos con posible actividad insecticida a partir de cianobacterias del Caribe colombiano 54 Química y ciencias afines / Chemistry 57 Ciencias de la vida; Biología / Life sciences; biology Cianobacterias Aedes aegypti Larvicida AChEI Artemia salina Cyanobacteria Lyngbya Moorea Peptides
title_short	Búsqueda de compuestos con posible actividad insecticida a partir de cianobacterias del Caribe colombiano
title_full	Búsqueda de compuestos con posible actividad insecticida a partir de cianobacterias del Caribe colombiano
title_fullStr	Búsqueda de compuestos con posible actividad insecticida a partir de cianobacterias del Caribe colombiano
title_full_unstemmed	Búsqueda de compuestos con posible actividad insecticida a partir de cianobacterias del Caribe colombiano
title_sort	Búsqueda de compuestos con posible actividad insecticida a partir de cianobacterias del Caribe colombiano
dc.creator.fl_str_mv	Ayala Muñoz, Farja Isabel
dc.contributor.author.spa.fl_str_mv	Ayala Muñoz, Farja Isabel
dc.contributor.spa.fl_str_mv	Castellanos Hernández, Leonardo
dc.subject.ddc.spa.fl_str_mv	54 Química y ciencias afines / Chemistry 57 Ciencias de la vida; Biología / Life sciences; biology
topic	54 Química y ciencias afines / Chemistry 57 Ciencias de la vida; Biología / Life sciences; biology Cianobacterias Aedes aegypti Larvicida AChEI Artemia salina Cyanobacteria Lyngbya Moorea Peptides
dc.subject.proposal.spa.fl_str_mv	Cianobacterias Aedes aegypti Larvicida AChEI Artemia salina Cyanobacteria Lyngbya Moorea Peptides
description	Se estudiaron tres mats de cianobacterias usando fraccionamiento bioguiado con el ensayo larvicida contra Aedes aegypti. Como compuestos activos se aislaron ácidos grasos insaturados, dos nuevos análogos de dolastatina D y el ácido seco malyngólido (nuevo), también la neodysidenina que afectó el desarrollo larvario y un heptapéptido cíclico nuevo mostró actividad promisoria.
publishDate	2017
dc.date.issued.spa.fl_str_mv	2017-05-26
dc.date.accessioned.spa.fl_str_mv	2019-07-02T20:58:07Z
dc.date.available.spa.fl_str_mv	2019-07-02T20:58:07Z
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/62357
dc.identifier.eprints.spa.fl_str_mv	http://bdigital.unal.edu.co/61428/
url	https://repositorio.unal.edu.co/handle/unal/62357 http://bdigital.unal.edu.co/61428/
dc.language.iso.spa.fl_str_mv	spa
language	spa
dc.relation.ispartof.spa.fl_str_mv	Universidad Nacional de Colombia Sede Bogotá Facultad de Ciencias Departamento de Química Departamento de Química
dc.relation.references.spa.fl_str_mv	Ayala Muñoz, Farja Isabel (2017) Búsqueda de compuestos con posible actividad insecticida a partir de cianobacterias del Caribe colombiano. Maestría thesis, Universidad Nacional de Colombia - Sede Bogotá.
dc.rights.spa.fl_str_mv	Derechos reservados - Universidad Nacional de Colombia
dc.rights.coar.fl_str_mv	http://purl.org/coar/access_right/c_abf2
dc.rights.license.spa.fl_str_mv	Atribución-NoComercial 4.0 Internacional
dc.rights.uri.spa.fl_str_mv	http://creativecommons.org/licenses/by-nc/4.0/
dc.rights.accessrights.spa.fl_str_mv	info:eu-repo/semantics/openAccess
rights_invalid_str_mv	Atribución-NoComercial 4.0 Internacional Derechos reservados - Universidad Nacional de Colombia http://creativecommons.org/licenses/by-nc/4.0/ http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv	openAccess
dc.format.mimetype.spa.fl_str_mv	application/pdf
institution	Universidad Nacional de Colombia
bitstream.url.fl_str_mv	https://repositorio.unal.edu.co/bitstream/unal/62357/1/1019065341.2017.pdf https://repositorio.unal.edu.co/bitstream/unal/62357/2/1019065341.2017.pdf.jpg
bitstream.checksum.fl_str_mv	a0cbba421e5c46fb6b1ff543372145ba fcbcfbd2f9b6accdd0f09b1314021727
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repository.name.fl_str_mv	Repositorio Institucional Universidad Nacional de Colombia
repository.mail.fl_str_mv	repositorio_nal@unal.edu.co
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spelling	Atribución-NoComercial 4.0 InternacionalDerechos reservados - Universidad Nacional de Colombiahttp://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Castellanos Hernández, LeonardoAyala Muñoz, Farja Isabela1c8a084-2649-48ae-985a-1ead361922a43002019-07-02T20:58:07Z2019-07-02T20:58:07Z2017-05-26https://repositorio.unal.edu.co/handle/unal/62357http://bdigital.unal.edu.co/61428/Se estudiaron tres mats de cianobacterias usando fraccionamiento bioguiado con el ensayo larvicida contra Aedes aegypti. Como compuestos activos se aislaron ácidos grasos insaturados, dos nuevos análogos de dolastatina D y el ácido seco malyngólido (nuevo), también la neodysidenina que afectó el desarrollo larvario y un heptapéptido cíclico nuevo mostró actividad promisoria.Abstract: Aedes aegypti L. [Diptera: Culicidae] is the disease vector mosquitoe for dengue, chikungunya, zika and yellow fever. Recently, several epidemic outbreaks occurred in hydroxyisovaleric acid)-(2-methyl-3-aminobutanoic acid)-(Ileu)-(2-hydroxy-3- phenilpropanoic acid)) CB1 and cyclo(NMe-(Ala)-(2-hydroxyisovaleric acid)-(2- methyl-3-aminobutanoic acid)-(Leu)-(2-hydroxy-3-phenilpropanoic acid)) CB2. These peptides are new dolastatin D analogs. CB1 and CB2 showed a moderated larvicide bioactivity (58% mortality, 0.09 mM), low ecotoxicity (low A. saline mortality) and were not AChE inhibitors. In addition, miristic acid (1), palmitic acid (2) and methyl palmitate (3) were identified by GC-MS from FI and FII fractions. Only compound 1 exhibited a moderated larvicide activity, but resulted to be toxic for A. saline. A second cyanobacteria mat identifyed as Lyngbya sp. (IBUN-02213) was also studied. From the active BuOH fraction (FB) a single compound was identified as (2R,5S)- malyngolide seco acid (CB3) by NMR and LC-(+)-HRESIMS data. This compound was previously obtained as a product of malyngolide basic hydrolysis, but was never reported as a natural product before. Then, this is the first time malyngolide seco acid is isolated as a secondary metabolite. In addition, malyngolide (CB4) was also isolated from this mat FD fraction. Malyngolide mat producer could be a new cyanobacterial gender among Lyngbya gender taxonomical reclassification. Compounds 1-3, methyl miristate (4), heptadecene (5) and phytone (6) were identified by GC-MS from FD. Compound 7 1-acetoxy-3-acetoxymethyl-7,11,15-trimethylhexadec-2,6,10,14- tetraene was detected by LC-HRESIMS of the same mat. The bioactivity assays for these compounds showed a moderated larvicide activity of CB3 along with a low toxicity against A. salina and probably AChE inhibition is its action mode. CB4 was not larvicide but showed a high A. saline lethality. This suggest that CB3 could be a good larvicida with no ecotoxic effects and it is obtained in high yields. Finally, the FD fraction of Moorea producens mat (IBUN-03496) exhibited a high larvae mortality (100% at 50 μg/well and 30% at 10 μg/well). Chemical analysis by GC-MS allowed identifing compounds 1-4 (also isolated from IBUN-02213), methyl stearate (8), methyl palmitoleate (9), mehtyl oleate (10) and crinasterol (12). Cholesterol (11), clionasterol (13) and campesterol (14) were isolated and elucidated by NMR and GCMS analysis. Additionally, a cis monounsaturated fatty acid showed a potent larvicide Colombia and worldwide. Control strategies focused on vector larvae control and are a global concern for these diseases prevention. Therefore, in this study, our aim was to isolate larvicide compounds against Ae. aegypti from Colombian Caribbean cyanobacterial mats. As a first step, 16 cyanobacterial mats were extracted with DCM/MeOH (1:1). Then, crude extract was fractionated by L-L partition in order to obtain a dichlorometane (FD) and buthanol (FB) fractions. All FD and FB fractions were evaluated in 3 different bioassays: larvicide assay against Ae. aegypti; ecotoxicity assay against Artemia salina and acetylcholinesterase inhibition assay as an approach to describe the possible action mode. In general terms, FD fractions showed to be more active than FB fractions. In addition, mats from the same species collected in different years exhibited different larvicide bioactivity (i.e. Phormidium submembranaceum /Symploca hynoides mats), as well as the ones that were collected at the same time in different locations (i.e. Moorea producens mats). As a result, three mats were selected for chemical studying according to bioassays results. A cyanobacterial mat identifyed as Phormidium sp. (IBUN-02224) was fractionated using a DIOL cartridge (mixtures hexane/ethyl acetate/MeOH, FI-FV), and FIII fraction showed larvicide activity along with a low letalithy over A. salina nauplii. This suggest that this fraction could control larvae with no ecotoxical effects. On the other hand, FIII did not show acetylcholinesterase inhibition, which is an advantage because insects have already developed insecticide resistance by AChE modification. FIII fraction purification yielded two new cyclic depsypeptides identifyed as cyclo(NMe-(Ala)-(2-hydroxyisovaleric acid)-(2-methyl-3-aminobutanoic acid)-(Ileu)-(2-hydroxy-3- phenilpropanoic acid)) CB1 and cyclo(NMe-(Ala)-(2-hydroxyisovaleric acid)-(2- methyl-3-aminobutanoic acid)-(Leu)-(2-hydroxy-3-phenilpropanoic acid)) CB2. These peptides are new dolastatin D analogs. CB1 and CB2 showed a moderated larvicide bioactivity (58% mortality, 0.09 mM), low ecotoxicity (low A. saline mortality) and were not AChE inhibitors. In addition, miristic acid (1), palmitic acid (2) and methyl palmitate (3) were identified by GC-MS from FI and FII fractions. Only compound 1 exhibited a moderated larvicide activity, but resulted to be toxic for A. saline. A second cyanobacteria mat identifyed as Lyngbya sp. (IBUN-02213) was also studied. From the active BuOH fraction (FB) a single compound was identified as (2R,5S)- malyngolide seco acid (CB3) by NMR and LC-(+)-HRESIMS data. This compound was previously obtained as a product of malyngolide basic hydrolysis, but was never reported as a natural product before. Then, this is the first time malyngolide seco acid is isolated as a secondary metabolite. In addition, malyngolide (CB4) was also isolated from this mat FD fraction. Malyngolide mat producer could be a new cyanobacterial gender among Lyngbya gender taxonomical reclassification. Compounds 1-3, methyl miristate (4), heptadecene (5) and phytone (6) were identified by GC-MS from FD. Compound 7 1-acetoxy-3-acetoxymethyl-7,11,15-trimethylhexadec-2,6,10,14- tetraene was detected by LC-HRESIMS of the same mat. The bioactivity assays for these compounds showed a moderated larvicide activity of CB3 along with a low toxicity against A. salina and probably AChE inhibition is its action mode. CB4 was not larvicide but showed a high A. saline lethality. This suggest that CB3 could be a good larvicida with no ecotoxic effects and it is obtained in high yields. Finally, the FD fraction of Moorea producens mat (IBUN-03496) exhibited a high larvae mortality (100% at 50 μg/well and 30% at 10 μg/well). Chemical analysis by GC-MS allowed identifing compounds 1-4 (also isolated from IBUN-02213), methyl stearate (8), methyl palmitoleate (9), mehtyl oleate (10) and crinasterol (12). Cholesterol (11), clionasterol (13) and campesterol (14) were isolated and elucidated by NMR and GCMS analysis. Additionally, a cis monounsaturated fatty acid showed a potent larvicide activity. Two peptides named neodysidenin (CB5) and the novel 10- dechloroneodysidenine (CB6) were isolated and their structures were proposed by NMR and LC-(+)-HRESIMS. From the most active fraction, a new compound CB8 (1mg) was isolated. It was identified as a cyclic depsipeptide cyclo((Dhoya)-(Thr)-NMe- (OMe-Tyr)-(Val)-(3,5-diaminopentanoic acid)-NMe-(Ileu)-(Leucic acid)). Dhoya is a very uncommon hydroxiacid that has been previously reported in cianobacterial compounds, and β-aminoacid 3,5-diaminopentanoic acid is found in a marine natural product for the first time. Regarding the results in the bioactivity tests monounsaturated fatty acids, as oleic acid, exhibited potent larvicide activity with low A. saline toxicity and no activity in AChE inhibition test. Neodysidenina showed a low larvicide activity but a larvae development disruption was observed. This research work shows the high biodiversity of cyanobacterial compounds with potencial use as larvicides controllers. Additonally, this thesis results contribute to chemiotaxonomy of Caribbean cyanobacterial mats, showing the importance of this taxonomical approach in biorpospection studies.Maestríaapplication/pdfspaUniversidad Nacional de Colombia Sede Bogotá Facultad de Ciencias Departamento de QuímicaDepartamento de QuímicaAyala Muñoz, Farja Isabel (2017) Búsqueda de compuestos con posible actividad insecticida a partir de cianobacterias del Caribe colombiano. Maestría thesis, Universidad Nacional de Colombia - Sede Bogotá.54 Química y ciencias afines / Chemistry57 Ciencias de la vida; Biología / Life sciences; biologyCianobacteriasAedes aegyptiLarvicidaAChEIArtemia salinaCyanobacteriaLyngbyaMooreaPeptidesBúsqueda de compuestos con posible actividad insecticida a partir de cianobacterias del Caribe colombianoTrabajo de grado - Maestríainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TMORIGINAL1019065341.2017.pdfapplication/pdf7938253https://repositorio.unal.edu.co/bitstream/unal/62357/1/1019065341.2017.pdfa0cbba421e5c46fb6b1ff543372145baMD51THUMBNAIL1019065341.2017.pdf.jpg1019065341.2017.pdf.jpgGenerated Thumbnailimage/jpeg5045https://repositorio.unal.edu.co/bitstream/unal/62357/2/1019065341.2017.pdf.jpgfcbcfbd2f9b6accdd0f09b1314021727MD52unal/62357oai:repositorio.unal.edu.co:unal/623572024-04-23 23:09:32.521Repositorio Institucional Universidad Nacional de Colombiarepositorio_nal@unal.edu.co

Búsqueda de compuestos con posible actividad insecticida a partir de cianobacterias del Caribe colombiano

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