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QSAR study of anti-Human African Trypanosomiasis activity for 2-phenylimidazopyridines derivatives using DFT and Lipinski's descriptors

The quantitative structure-activity relationship (QSAR) of sixty 2-phenylimidazopyridines derivatives with anti-Human African Trypanosomiasis (anti-HAT) activity has been studied by using the density functional theory (DFT) and statistical methods. Becke's three-parameter hybrid method and the...

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Autores principales: Chtita, Samir, Ghamali, Mounir, Ousaa, Abdellah, Aouidate, Adnane, Belhassan, Assia, Taourati, Abdelali Idrissi, Masand, Vijay Hariram, Bouachrine, Mohammed, Lakhlifi, Tahar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407088/
https://www.ncbi.nlm.nih.gov/pubmed/30899832
http://dx.doi.org/10.1016/j.heliyon.2019.e01304
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author Chtita, Samir
Ghamali, Mounir
Ousaa, Abdellah
Aouidate, Adnane
Belhassan, Assia
Taourati, Abdelali Idrissi
Masand, Vijay Hariram
Bouachrine, Mohammed
Lakhlifi, Tahar
author_facet Chtita, Samir
Ghamali, Mounir
Ousaa, Abdellah
Aouidate, Adnane
Belhassan, Assia
Taourati, Abdelali Idrissi
Masand, Vijay Hariram
Bouachrine, Mohammed
Lakhlifi, Tahar
author_sort Chtita, Samir
collection PubMed
description The quantitative structure-activity relationship (QSAR) of sixty 2-phenylimidazopyridines derivatives with anti-Human African Trypanosomiasis (anti-HAT) activity has been studied by using the density functional theory (DFT) and statistical methods. Becke's three-parameter hybrid method and the Lee-Yang-Parr B3LYP functional employing 6–31G(d) basis set are used to calculate quantum chemical descriptors using Gaussian 03W software, and the five Lipinski's parameters were calculated using ChemOffice software. In order to obtain robust and reliable QSAR model, the original dataset was randomly divided into training and prediction sets comprising 48 and 12 compounds, respectively. An optimal model for the training set with significant statistical quality was established. The same model was further applied to predict pEC(50) values of the 12 compounds in the test set, further showing that this QSAR model has high predictive ability. It is very interesting to find that the anti-HAT of these compounds appear to be mainly governed by four factors, i.e., the number of H-bond donors, the lowest unoccupied molecular orbital energy, the molecular weight and the octanol/water partition coefficient. Here the possible action mechanism of these compounds was analysed and discussed, in particular, important structural requirements for great anti-HAT activity will be by increasing molecular size and substitute the 2-phenylimidazopyridines derivatives with polar, ionic, stronger accepting electron ability group and heteroatoms attached to one or more hydrogen atoms. Based on this proposed QSAR model, some new compounds with higher anti-HAT activities have been theoretically designed. Such results can offer useful theoretical references for future experimental works.
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spelling pubmed-64070882019-03-21 QSAR study of anti-Human African Trypanosomiasis activity for 2-phenylimidazopyridines derivatives using DFT and Lipinski's descriptors Chtita, Samir Ghamali, Mounir Ousaa, Abdellah Aouidate, Adnane Belhassan, Assia Taourati, Abdelali Idrissi Masand, Vijay Hariram Bouachrine, Mohammed Lakhlifi, Tahar Heliyon Article The quantitative structure-activity relationship (QSAR) of sixty 2-phenylimidazopyridines derivatives with anti-Human African Trypanosomiasis (anti-HAT) activity has been studied by using the density functional theory (DFT) and statistical methods. Becke's three-parameter hybrid method and the Lee-Yang-Parr B3LYP functional employing 6–31G(d) basis set are used to calculate quantum chemical descriptors using Gaussian 03W software, and the five Lipinski's parameters were calculated using ChemOffice software. In order to obtain robust and reliable QSAR model, the original dataset was randomly divided into training and prediction sets comprising 48 and 12 compounds, respectively. An optimal model for the training set with significant statistical quality was established. The same model was further applied to predict pEC(50) values of the 12 compounds in the test set, further showing that this QSAR model has high predictive ability. It is very interesting to find that the anti-HAT of these compounds appear to be mainly governed by four factors, i.e., the number of H-bond donors, the lowest unoccupied molecular orbital energy, the molecular weight and the octanol/water partition coefficient. Here the possible action mechanism of these compounds was analysed and discussed, in particular, important structural requirements for great anti-HAT activity will be by increasing molecular size and substitute the 2-phenylimidazopyridines derivatives with polar, ionic, stronger accepting electron ability group and heteroatoms attached to one or more hydrogen atoms. Based on this proposed QSAR model, some new compounds with higher anti-HAT activities have been theoretically designed. Such results can offer useful theoretical references for future experimental works. Elsevier 2019-03-07 /pmc/articles/PMC6407088/ /pubmed/30899832 http://dx.doi.org/10.1016/j.heliyon.2019.e01304 Text en © 2019 The Authors. Published by Elsevier Ltd. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Chtita, Samir
Ghamali, Mounir
Ousaa, Abdellah
Aouidate, Adnane
Belhassan, Assia
Taourati, Abdelali Idrissi
Masand, Vijay Hariram
Bouachrine, Mohammed
Lakhlifi, Tahar
QSAR study of anti-Human African Trypanosomiasis activity for 2-phenylimidazopyridines derivatives using DFT and Lipinski's descriptors
title QSAR study of anti-Human African Trypanosomiasis activity for 2-phenylimidazopyridines derivatives using DFT and Lipinski's descriptors
title_full QSAR study of anti-Human African Trypanosomiasis activity for 2-phenylimidazopyridines derivatives using DFT and Lipinski's descriptors
title_fullStr QSAR study of anti-Human African Trypanosomiasis activity for 2-phenylimidazopyridines derivatives using DFT and Lipinski's descriptors
title_full_unstemmed QSAR study of anti-Human African Trypanosomiasis activity for 2-phenylimidazopyridines derivatives using DFT and Lipinski's descriptors
title_short QSAR study of anti-Human African Trypanosomiasis activity for 2-phenylimidazopyridines derivatives using DFT and Lipinski's descriptors
title_sort qsar study of anti-human african trypanosomiasis activity for 2-phenylimidazopyridines derivatives using dft and lipinski's descriptors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407088/
https://www.ncbi.nlm.nih.gov/pubmed/30899832
http://dx.doi.org/10.1016/j.heliyon.2019.e01304
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