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Application of 4D-QSAR Studies to a Series of Raloxifene Analogs and Design of Potential Selective Estrogen Receptor Modulators

Four-dimensional quantitative structure-activity relationship (4D-QSAR) analysis was applied on a series of 54 2-arylbenzothiophene derivatives, synthesized by Grese and coworkers, based on raloxifene (an estrogen receptor-alpha antagonist), and evaluated as ERα ligands and as inhibitors of estrogen...

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Autores principales: Sodero, Ana Carolina Rennó, Romeiro, Nelilma Correia, da Cunha, Elaine Fontes Ferreira, de Oliveira Magalhães, Uiaran, de Alencastro, Ricardo Bicca, Rodrigues, Carlos Rangel, Cabral, Lúcio Mendes, Castro, Helena Carla, Albuquerque, Magaly Girão
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6268799/
https://www.ncbi.nlm.nih.gov/pubmed/22706372
http://dx.doi.org/10.3390/molecules17067415
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author Sodero, Ana Carolina Rennó
Romeiro, Nelilma Correia
da Cunha, Elaine Fontes Ferreira
de Oliveira Magalhães, Uiaran
de Alencastro, Ricardo Bicca
Rodrigues, Carlos Rangel
Cabral, Lúcio Mendes
Castro, Helena Carla
Albuquerque, Magaly Girão
author_facet Sodero, Ana Carolina Rennó
Romeiro, Nelilma Correia
da Cunha, Elaine Fontes Ferreira
de Oliveira Magalhães, Uiaran
de Alencastro, Ricardo Bicca
Rodrigues, Carlos Rangel
Cabral, Lúcio Mendes
Castro, Helena Carla
Albuquerque, Magaly Girão
author_sort Sodero, Ana Carolina Rennó
collection PubMed
description Four-dimensional quantitative structure-activity relationship (4D-QSAR) analysis was applied on a series of 54 2-arylbenzothiophene derivatives, synthesized by Grese and coworkers, based on raloxifene (an estrogen receptor-alpha antagonist), and evaluated as ERα ligands and as inhibitors of estrogen-stimulated proliferation of MCF-7 breast cancer cells. The conformations of each analogue, sampled from a molecular dynamics simulation, were placed in a grid cell lattice according to three trial alignments, considering two grid cell sizes (1.0 and 2.0 Å). The QSAR equations, generated by a combined scheme of genetic algorithms (GA) and partial least squares (PLS) regression, were evaluated by “leave-one-out” cross-validation, using a training set of 41 compounds. External validation was performed using a test set of 13 compounds. The obtained 4D-QSAR models are in agreement with the proposed mechanism of action for raloxifene. This study allowed a quantitative prediction of compounds’ potency and supported the design of new raloxifene analogs.
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spelling pubmed-62687992018-12-12 Application of 4D-QSAR Studies to a Series of Raloxifene Analogs and Design of Potential Selective Estrogen Receptor Modulators Sodero, Ana Carolina Rennó Romeiro, Nelilma Correia da Cunha, Elaine Fontes Ferreira de Oliveira Magalhães, Uiaran de Alencastro, Ricardo Bicca Rodrigues, Carlos Rangel Cabral, Lúcio Mendes Castro, Helena Carla Albuquerque, Magaly Girão Molecules Article Four-dimensional quantitative structure-activity relationship (4D-QSAR) analysis was applied on a series of 54 2-arylbenzothiophene derivatives, synthesized by Grese and coworkers, based on raloxifene (an estrogen receptor-alpha antagonist), and evaluated as ERα ligands and as inhibitors of estrogen-stimulated proliferation of MCF-7 breast cancer cells. The conformations of each analogue, sampled from a molecular dynamics simulation, were placed in a grid cell lattice according to three trial alignments, considering two grid cell sizes (1.0 and 2.0 Å). The QSAR equations, generated by a combined scheme of genetic algorithms (GA) and partial least squares (PLS) regression, were evaluated by “leave-one-out” cross-validation, using a training set of 41 compounds. External validation was performed using a test set of 13 compounds. The obtained 4D-QSAR models are in agreement with the proposed mechanism of action for raloxifene. This study allowed a quantitative prediction of compounds’ potency and supported the design of new raloxifene analogs. MDPI 2012-06-15 /pmc/articles/PMC6268799/ /pubmed/22706372 http://dx.doi.org/10.3390/molecules17067415 Text en © 2012 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Sodero, Ana Carolina Rennó
Romeiro, Nelilma Correia
da Cunha, Elaine Fontes Ferreira
de Oliveira Magalhães, Uiaran
de Alencastro, Ricardo Bicca
Rodrigues, Carlos Rangel
Cabral, Lúcio Mendes
Castro, Helena Carla
Albuquerque, Magaly Girão
Application of 4D-QSAR Studies to a Series of Raloxifene Analogs and Design of Potential Selective Estrogen Receptor Modulators
title Application of 4D-QSAR Studies to a Series of Raloxifene Analogs and Design of Potential Selective Estrogen Receptor Modulators
title_full Application of 4D-QSAR Studies to a Series of Raloxifene Analogs and Design of Potential Selective Estrogen Receptor Modulators
title_fullStr Application of 4D-QSAR Studies to a Series of Raloxifene Analogs and Design of Potential Selective Estrogen Receptor Modulators
title_full_unstemmed Application of 4D-QSAR Studies to a Series of Raloxifene Analogs and Design of Potential Selective Estrogen Receptor Modulators
title_short Application of 4D-QSAR Studies to a Series of Raloxifene Analogs and Design of Potential Selective Estrogen Receptor Modulators
title_sort application of 4d-qsar studies to a series of raloxifene analogs and design of potential selective estrogen receptor modulators
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6268799/
https://www.ncbi.nlm.nih.gov/pubmed/22706372
http://dx.doi.org/10.3390/molecules17067415
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