Computational fishing of new DNA methyltransferase inhibitors from natural products
DNA methyltransferase inhibitors (DNMTis) have become an alternative for cancer therapies. However, only two DNMTis have been approved as anticancer drugs, although with some restrictions. Natural products (NPs) are a promising source of drugs. In order to find NPs with novel chemotypes as DNMTis, 47 compounds with known activity against these enzymes were used to build a LDA-based QSAR model for active/inactive molecules (93% accuracy) based on molecular descriptors. This classifier was employed to identify potential DNMTis on 800 NPs from NatProd Collection. 447 selected compounds were docked on two human DNA methyltransferase (DNMT) structures (PDB codes: 3SWR and 2QRV) using AutoDock Vina and Surflex-Dock, prioritizing according to their score values, contact patterns at 4 ˚A and molecular diversity. Six consensus NPs were identified as virtual hits against DNMTs, including 9,10-dihydro- 12-hydroxygambogic, phloridzin, 2’,4’-dihydroxychalcone 4’-glucoside, daunorubicin, pyrromycin and centaurein. This method is an innovative computational strategy for identifying DNMTis, useful in the identification of potent and selective anticancer drugs.
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2015-06
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Subjects: | Biología vegetal, Aceites vegetales, Productos químicos, Anticancer, Screening, QSAR, Docking, Cluster, Biotecnología, Tecnología química, Química agrícola, |
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dig-minciencias-co-20.500.14143-341662023-11-29T12:29:20Z Computational fishing of new DNA methyltransferase inhibitors from natural products Maldonado Rojas, Wilson Olivero Vebel, Jesús Marrero Ponce, Yovani Biología vegetal Aceites vegetales Productos químicos Anticancer Screening QSAR Docking Cluster Biotecnología Tecnología química Química agrícola DNA methyltransferase inhibitors (DNMTis) have become an alternative for cancer therapies. However, only two DNMTis have been approved as anticancer drugs, although with some restrictions. Natural products (NPs) are a promising source of drugs. In order to find NPs with novel chemotypes as DNMTis, 47 compounds with known activity against these enzymes were used to build a LDA-based QSAR model for active/inactive molecules (93% accuracy) based on molecular descriptors. This classifier was employed to identify potential DNMTis on 800 NPs from NatProd Collection. 447 selected compounds were docked on two human DNA methyltransferase (DNMT) structures (PDB codes: 3SWR and 2QRV) using AutoDock Vina and Surflex-Dock, prioritizing according to their score values, contact patterns at 4 ˚A and molecular diversity. Six consensus NPs were identified as virtual hits against DNMTs, including 9,10-dihydro- 12-hydroxygambogic, phloridzin, 2’,4’-dihydroxychalcone 4’-glucoside, daunorubicin, pyrromycin and centaurein. This method is an innovative computational strategy for identifying DNMTis, useful in the identification of potent and selective anticancer drugs. Departamento Administrativo de Ciencia, Tecnología e Innovación [CO] Colciencias 5507-543-31904 Programa: Bioprospección y desarrollo de ingredientes naturales para las industrias cosmética, farmacéutica y de productos de aseo con base en la biodiversidad colombiana no 2019-04-01T00:03:06Z 2019-04-01T00:03:06Z 2015-06 info:eu-repo/date/embargoEnd/2024-01-31 Artículo científico info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article 1093-3263 http://repositorio.colciencias.gov.co/handle/11146/34166 Contiene 109 referencias bibliográficas. Véase documento adjunto 10.1016/j.jmgm.2015.04.010 eng 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> info:eu-repo/semantics/embargoedAccess pdf 12 páginas application/pdf Colombia Journal of Molecular Graphics and Modelling 60 (2015) 43–54 |
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Biología vegetal Aceites vegetales Productos químicos Anticancer Screening QSAR Docking Cluster Biotecnología Tecnología química Química agrícola Biología vegetal Aceites vegetales Productos químicos Anticancer Screening QSAR Docking Cluster Biotecnología Tecnología química Química agrícola |
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Biología vegetal Aceites vegetales Productos químicos Anticancer Screening QSAR Docking Cluster Biotecnología Tecnología química Química agrícola Biología vegetal Aceites vegetales Productos químicos Anticancer Screening QSAR Docking Cluster Biotecnología Tecnología química Química agrícola Maldonado Rojas, Wilson Olivero Vebel, Jesús Marrero Ponce, Yovani Computational fishing of new DNA methyltransferase inhibitors from natural products |
description |
DNA methyltransferase inhibitors (DNMTis) have become an alternative for cancer therapies. However, only two DNMTis have been approved as anticancer drugs, although with some restrictions. Natural products (NPs) are a promising source of drugs. In order to find NPs with novel chemotypes as DNMTis, 47 compounds with known activity against these enzymes were used to build a LDA-based QSAR model for active/inactive molecules (93% accuracy) based on molecular descriptors. This classifier was employed to identify potential DNMTis on 800 NPs from NatProd Collection. 447 selected compounds were docked on two human DNA methyltransferase (DNMT) structures (PDB codes: 3SWR and 2QRV) using AutoDock Vina and Surflex-Dock, prioritizing according to their score values, contact patterns at 4 ˚A and molecular diversity. Six consensus NPs were identified as virtual hits against DNMTs, including 9,10-dihydro- 12-hydroxygambogic, phloridzin, 2’,4’-dihydroxychalcone 4’-glucoside, daunorubicin, pyrromycin and centaurein. This method is an innovative computational strategy for identifying DNMTis, useful in the identification of potent and selective anticancer drugs. |
format |
Artículo científico |
topic_facet |
Biología vegetal Aceites vegetales Productos químicos Anticancer Screening QSAR Docking Cluster Biotecnología Tecnología química Química agrícola |
author |
Maldonado Rojas, Wilson Olivero Vebel, Jesús Marrero Ponce, Yovani |
author_facet |
Maldonado Rojas, Wilson Olivero Vebel, Jesús Marrero Ponce, Yovani |
author_sort |
Maldonado Rojas, Wilson |
title |
Computational fishing of new DNA methyltransferase inhibitors from natural products |
title_short |
Computational fishing of new DNA methyltransferase inhibitors from natural products |
title_full |
Computational fishing of new DNA methyltransferase inhibitors from natural products |
title_fullStr |
Computational fishing of new DNA methyltransferase inhibitors from natural products |
title_full_unstemmed |
Computational fishing of new DNA methyltransferase inhibitors from natural products |
title_sort |
computational fishing of new dna methyltransferase inhibitors from natural products |
publishDate |
2015-06 |
url |
http://repositorio.colciencias.gov.co/handle/11146/34166 |
work_keys_str_mv |
AT maldonadorojaswilson computationalfishingofnewdnamethyltransferaseinhibitorsfromnaturalproducts AT oliverovebeljesus computationalfishingofnewdnamethyltransferaseinhibitorsfromnaturalproducts AT marreroponceyovani computationalfishingofnewdnamethyltransferaseinhibitorsfromnaturalproducts |
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1798162125265305600 |