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Pyridine-N-Oxide Alkaloids from Allium stipitatum and Their Synthetic Disulfide Analogs as Potential Drug Candidates against Mycobacterium tuberculosis: A Molecular Docking, QSBAR, and ADMET Prediction Approach
In this study, we consider pyridine-N-oxide alkaloids from Allium stipitatum and their synthetic disulfide analogs (PDAs) as candidates for next-generational antimycobacterial agents, in light of growing resistance to existing conventional therapies. In silico studies involving molecular docking sim...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Hindawi
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9568345/ https://www.ncbi.nlm.nih.gov/pubmed/36246961 http://dx.doi.org/10.1155/2022/6261528 |
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author | Amengor, Cedric Dzidzor Kodjo Orman, Emmanuel Danquah, Cynthia Amaning Ben, Inemesit Okon Biniyam, Prince Danan Harley, Benjamin Kingsley |
author_facet | Amengor, Cedric Dzidzor Kodjo Orman, Emmanuel Danquah, Cynthia Amaning Ben, Inemesit Okon Biniyam, Prince Danan Harley, Benjamin Kingsley |
author_sort | Amengor, Cedric Dzidzor Kodjo |
collection | PubMed |
description | In this study, we consider pyridine-N-oxide alkaloids from Allium stipitatum and their synthetic disulfide analogs (PDAs) as candidates for next-generational antimycobacterial agents, in light of growing resistance to existing conventional therapies. In silico studies involving molecular docking simulations of 12 PDAs were carried out against 7 Mycobacterium tuberculosis target proteins (MTs) to determine their theoretical binding affinities. Compounds A3, A6, and B9 demonstrated stronger binding affinities on similar MTs. Molecular descriptors (MDs) describing structural and physicochemical properties of the compounds were also calculated using ChemDes, explored using Pearson's correlation analysis, and principal component analysis (PCA) in comparison with MDs from conventional antitubercular medicines. The PDAs possessed similar scores as isoniazid and pyrazinamide. The MDs were also used to conduct a quantitative structure-binding affinity relationship (QSBAR) study by building good fit and significant models through principal component regression (PCR) and partial least squares regression (PLSR). Leave-one-out cross-validation was adopted in the PLSR, resulting in good predictive models on all MTs (range of R(2) = 0.7541‐0.8992; range of Q(2) = 0.6183‐0.8162). Both PCR and PLSR models predicted the significant effects of ndonr, Hy, Mol wt, nhev, nring, ndb, Log P, W, Pol, ISIZ, TIAC, Getov, and UI on the binding of ligands to the MTs. In silico prediction of PDAs' ADMET profiles was conducted with QikProp utility. The ADMET profiles of the compounds were favorable. The outcome of the current study strengthens the significance of these compounds as promising lead candidates for the treatment of multidrug-resistant tuberculosis. |
format | Online Article Text |
id | pubmed-9568345 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-95683452022-10-15 Pyridine-N-Oxide Alkaloids from Allium stipitatum and Their Synthetic Disulfide Analogs as Potential Drug Candidates against Mycobacterium tuberculosis: A Molecular Docking, QSBAR, and ADMET Prediction Approach Amengor, Cedric Dzidzor Kodjo Orman, Emmanuel Danquah, Cynthia Amaning Ben, Inemesit Okon Biniyam, Prince Danan Harley, Benjamin Kingsley Biomed Res Int Research Article In this study, we consider pyridine-N-oxide alkaloids from Allium stipitatum and their synthetic disulfide analogs (PDAs) as candidates for next-generational antimycobacterial agents, in light of growing resistance to existing conventional therapies. In silico studies involving molecular docking simulations of 12 PDAs were carried out against 7 Mycobacterium tuberculosis target proteins (MTs) to determine their theoretical binding affinities. Compounds A3, A6, and B9 demonstrated stronger binding affinities on similar MTs. Molecular descriptors (MDs) describing structural and physicochemical properties of the compounds were also calculated using ChemDes, explored using Pearson's correlation analysis, and principal component analysis (PCA) in comparison with MDs from conventional antitubercular medicines. The PDAs possessed similar scores as isoniazid and pyrazinamide. The MDs were also used to conduct a quantitative structure-binding affinity relationship (QSBAR) study by building good fit and significant models through principal component regression (PCR) and partial least squares regression (PLSR). Leave-one-out cross-validation was adopted in the PLSR, resulting in good predictive models on all MTs (range of R(2) = 0.7541‐0.8992; range of Q(2) = 0.6183‐0.8162). Both PCR and PLSR models predicted the significant effects of ndonr, Hy, Mol wt, nhev, nring, ndb, Log P, W, Pol, ISIZ, TIAC, Getov, and UI on the binding of ligands to the MTs. In silico prediction of PDAs' ADMET profiles was conducted with QikProp utility. The ADMET profiles of the compounds were favorable. The outcome of the current study strengthens the significance of these compounds as promising lead candidates for the treatment of multidrug-resistant tuberculosis. Hindawi 2022-10-07 /pmc/articles/PMC9568345/ /pubmed/36246961 http://dx.doi.org/10.1155/2022/6261528 Text en Copyright © 2022 Cedric Dzidzor Kodjo Amengor et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Amengor, Cedric Dzidzor Kodjo Orman, Emmanuel Danquah, Cynthia Amaning Ben, Inemesit Okon Biniyam, Prince Danan Harley, Benjamin Kingsley Pyridine-N-Oxide Alkaloids from Allium stipitatum and Their Synthetic Disulfide Analogs as Potential Drug Candidates against Mycobacterium tuberculosis: A Molecular Docking, QSBAR, and ADMET Prediction Approach |
title | Pyridine-N-Oxide Alkaloids from Allium stipitatum and Their Synthetic Disulfide Analogs as Potential Drug Candidates against Mycobacterium tuberculosis: A Molecular Docking, QSBAR, and ADMET Prediction Approach |
title_full | Pyridine-N-Oxide Alkaloids from Allium stipitatum and Their Synthetic Disulfide Analogs as Potential Drug Candidates against Mycobacterium tuberculosis: A Molecular Docking, QSBAR, and ADMET Prediction Approach |
title_fullStr | Pyridine-N-Oxide Alkaloids from Allium stipitatum and Their Synthetic Disulfide Analogs as Potential Drug Candidates against Mycobacterium tuberculosis: A Molecular Docking, QSBAR, and ADMET Prediction Approach |
title_full_unstemmed | Pyridine-N-Oxide Alkaloids from Allium stipitatum and Their Synthetic Disulfide Analogs as Potential Drug Candidates against Mycobacterium tuberculosis: A Molecular Docking, QSBAR, and ADMET Prediction Approach |
title_short | Pyridine-N-Oxide Alkaloids from Allium stipitatum and Their Synthetic Disulfide Analogs as Potential Drug Candidates against Mycobacterium tuberculosis: A Molecular Docking, QSBAR, and ADMET Prediction Approach |
title_sort | pyridine-n-oxide alkaloids from allium stipitatum and their synthetic disulfide analogs as potential drug candidates against mycobacterium tuberculosis: a molecular docking, qsbar, and admet prediction approach |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9568345/ https://www.ncbi.nlm.nih.gov/pubmed/36246961 http://dx.doi.org/10.1155/2022/6261528 |
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