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Identification of Electronic and Structural Descriptors of Adenosine Analogues Related to Inhibition of Leishmanial Glyceraldehyde-3-Phosphate Dehydrogenase
Quantitative structure–activity relationship (QSAR) studies were performed in order to identify molecular features responsible for the antileishmanial activity of 61 adenosine analogues acting as inhibitors of the enzyme glyceraldehyde 3-phosphate dehydrogenase of Leishmania mexicana (LmGAPDH). Dens...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269754/ https://www.ncbi.nlm.nih.gov/pubmed/23629757 http://dx.doi.org/10.3390/molecules18055032 |
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author | Lozano, Norka B. H. Oliveira, Rafael F. Weber, Karen C. Honorio, Kathia M. Guido, Rafael V. Andricopulo, Adriano D. Da Silva, Albérico B. F. |
author_facet | Lozano, Norka B. H. Oliveira, Rafael F. Weber, Karen C. Honorio, Kathia M. Guido, Rafael V. Andricopulo, Adriano D. Da Silva, Albérico B. F. |
author_sort | Lozano, Norka B. H. |
collection | PubMed |
description | Quantitative structure–activity relationship (QSAR) studies were performed in order to identify molecular features responsible for the antileishmanial activity of 61 adenosine analogues acting as inhibitors of the enzyme glyceraldehyde 3-phosphate dehydrogenase of Leishmania mexicana (LmGAPDH). Density functional theory (DFT) was employed to calculate quantum-chemical descriptors, while several structural descriptors were generated with Dragon 5.4. Variable selection was undertaken with the ordered predictor selection (OPS) algorithm, which provided a set with the most relevant descriptors to perform PLS, PCR and MLR regressions. Reliable and predictive models were obtained, as attested by their high correlation coefficients, as well as the agreement between predicted and experimental values for an external test set. Additional validation procedures were carried out, demonstrating that robust models were developed, providing helpful tools for the optimization of the antileishmanial activity of adenosine compounds. |
format | Online Article Text |
id | pubmed-6269754 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62697542018-12-14 Identification of Electronic and Structural Descriptors of Adenosine Analogues Related to Inhibition of Leishmanial Glyceraldehyde-3-Phosphate Dehydrogenase Lozano, Norka B. H. Oliveira, Rafael F. Weber, Karen C. Honorio, Kathia M. Guido, Rafael V. Andricopulo, Adriano D. Da Silva, Albérico B. F. Molecules Article Quantitative structure–activity relationship (QSAR) studies were performed in order to identify molecular features responsible for the antileishmanial activity of 61 adenosine analogues acting as inhibitors of the enzyme glyceraldehyde 3-phosphate dehydrogenase of Leishmania mexicana (LmGAPDH). Density functional theory (DFT) was employed to calculate quantum-chemical descriptors, while several structural descriptors were generated with Dragon 5.4. Variable selection was undertaken with the ordered predictor selection (OPS) algorithm, which provided a set with the most relevant descriptors to perform PLS, PCR and MLR regressions. Reliable and predictive models were obtained, as attested by their high correlation coefficients, as well as the agreement between predicted and experimental values for an external test set. Additional validation procedures were carried out, demonstrating that robust models were developed, providing helpful tools for the optimization of the antileishmanial activity of adenosine compounds. MDPI 2013-04-29 /pmc/articles/PMC6269754/ /pubmed/23629757 http://dx.doi.org/10.3390/molecules18055032 Text en © 2013 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 Lozano, Norka B. H. Oliveira, Rafael F. Weber, Karen C. Honorio, Kathia M. Guido, Rafael V. Andricopulo, Adriano D. Da Silva, Albérico B. F. Identification of Electronic and Structural Descriptors of Adenosine Analogues Related to Inhibition of Leishmanial Glyceraldehyde-3-Phosphate Dehydrogenase |
title | Identification of Electronic and Structural Descriptors of Adenosine Analogues Related to Inhibition of Leishmanial Glyceraldehyde-3-Phosphate Dehydrogenase |
title_full | Identification of Electronic and Structural Descriptors of Adenosine Analogues Related to Inhibition of Leishmanial Glyceraldehyde-3-Phosphate Dehydrogenase |
title_fullStr | Identification of Electronic and Structural Descriptors of Adenosine Analogues Related to Inhibition of Leishmanial Glyceraldehyde-3-Phosphate Dehydrogenase |
title_full_unstemmed | Identification of Electronic and Structural Descriptors of Adenosine Analogues Related to Inhibition of Leishmanial Glyceraldehyde-3-Phosphate Dehydrogenase |
title_short | Identification of Electronic and Structural Descriptors of Adenosine Analogues Related to Inhibition of Leishmanial Glyceraldehyde-3-Phosphate Dehydrogenase |
title_sort | identification of electronic and structural descriptors of adenosine analogues related to inhibition of leishmanial glyceraldehyde-3-phosphate dehydrogenase |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269754/ https://www.ncbi.nlm.nih.gov/pubmed/23629757 http://dx.doi.org/10.3390/molecules18055032 |
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