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Searching of new natural DNA methyltransferase inhibitors using computational approach

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dc.coverage.spatial Colombia es_CO
dc.creator Maldonado Rojas, Wilson
dc.creator Marrero Ponce, Yovani
dc.creator Olivero Vebel, Jesús
dc.date.accessioned 2019-04-02T14:42:38Z
dc.date.available 2019-04-02T14:42:38Z
dc.date.issued 2015
dc.identifier.uri http://repositorio.colciencias.gov.co/handle/11146/34217
dc.description Artículo pre-print es_CO
dc.description.abstract The searching of DNA methyltransferases inhibitors (DNMTs), therapeutic targets in cancer, is currently a scientific priority. However, only two DNMTs inhibitors have been approved as anticancer drugs, although with some restrictions. Natural products (NPs) are a promising source of drugs due to their wide molecular diversity and low toxicity. In order to find NPs with novel chemotypes for inhibitors of DNMTs, in this study an in silico searching was performed using a combination of QSAR and protein-ligand docking. A set of 47 compounds with known activity against these enzymes was used to construct a discriminating model of active/inactive molecules (93% accuracy), based on physicochemical descriptors generated by the DRAGON program. This classifier was used to identify potential DNMTs inhibitors on 800 NPs from the NatProd Collection (www.msdiscovery.com/natprod.html). 447 selected compounds were docked on two human DNMTs structures (DNMT1:3SWR and DNMT3A:2QRV) using AutoDock Vina and Surflex-Dock programs, with subsequent prioritization according to their score values, contact patterns at 4 Å and molecular diversity from clustering (k-means). Six NPs with novel chemotypes were identified as virtual hits against DNMTs, including 9,10-dihydro 12-hydroxygambogic, phloridzin, 2',4'-dihydroxychalcone 4'-glucoside, daunorubicin, pyrromycin and centaurein. The methodology proposed in this study is an innovative computational tool for identifying DNMT inhibitors, useful in the design of more potent and selective anticancer drugs. es_CO
dc.description.sponsorship Departamento Administrativo de Ciencia, Tecnología e Innovación [CO] Colciencias es_CO
dc.format pdf es_CO
dc.format.extent 36 páginas es_CO
dc.language.iso eng es_CO
dc.relation.ispartof Programa: Bioprospección y desarrollo de ingredientes naturales para las industrias cosmética, farmacéutica y de productos de aseo con base en la biodiversidad colombiana. La publicación completa está disponible en : <a href="http://repositorio.colciencias.gov.co/handle/11146/34163" target="blank">http://repositorio.colciencias.gov.co/handle/11146/34163</a> es_CO
dc.rights info:eu-repo/semantics/embargoedAccess es_CO
dc.title Searching of new natural DNA methyltransferase inhibitors using computational approach es_CO
dc.type info:eu-repo/semantics/other.generacióndecontenidos es_CO
dc.date.embargoEnd info:eu-repo/date/embargoEnd/2024-01-31 es_CO
dc.type.hasversion info:eu-repo/semantics/allowedVersion es_CO
dc.description.projectid 5507-543-31904 es_CO
col.date.proyecto 2018-01
col.programa.colciencias Programas de CT+I Ejecutados por Redes de Conocimiento es_CO
col.comunidadvinculada Comunidad científica colombiana es_CO
dc.creator.corporativo Bio-Red-CO-CENIVAM es_CO
dc.creator.corporativo Universidad de Cartagena, Unicartagena es_CO
dc.audience Investigadores es_CO
dc.description.projectname Programa: Bioprospección y desarrollo de ingredientes naturales para las industrias cosmética, farmacéutica y de productos de aseo con base en la biodiversidad colombiana es_CO
dc.description.isproject no es_CO
dc.creator.mail joliverov@unicartagena.edu.co es_CO
dc.identifier.bibliographicCitation Contiene 92 referencias bibliográficas. Véase documento adjunto es_CO
dc.subject.lemb Productos químicos es_CO
dc.subject.keyword Virtual screening
dc.subject.keyword DNA methyltransferase
dc.subject.keyword QSAR
dc.subject.keyword AutoDock Vina
dc.subject.keyword Surflex-Dock
dc.subject.keyword Anticancer drugs
dc.subject.spines Biología molecular es_CO
dc.subject.spines Aceites esenciales es_CO
dc.subject.spines Tecnología química es_CO
col.contrato 0572-2012 es_CO
col.tipo.esp Generación de contenidos impresos, radiales, audiovisuales, multimedia, virtuales y Creative Commons es_CO


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