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...
| Publicado en: | BioMed Research International pp. 1 - 15 |
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| Autores principales: | , , , , , |
| Formato: | equations & formulas pictorial research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
10/7/2022
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=159554503&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 159554503 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 23146133 FT2T jtl: BioMed Research International issn: 23146133 maglogo: N pubinfo: dt: 10/7/2022 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 159554503 159554503 159554503 10.1155/2022/6261528 159554503 ppf: 1 ppct: 14 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: 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. aug: au: Amengor, Cedric Dzidzor Kodjo Orman, Emmanuel Danquah, Cynthia Amaning Ben, Inemesit Okon Biniyam, Prince Danan Harley, Benjamin Kingsley affil: Department of Pharmaceutical Chemistry, School of Pharmacy, University of Health and Allied Sciences, Ho, Ghana sug: subj: Tuberculosis Drug Therapy Mycobacterium Tuberculosis Drug Effects Plant Extracts Pharmacodynamics Alkaloids Pharmacodynamics Sulfur Compounds Pharmacodynamics Molecular Docking Simulation Methods Antitubercular Agents Pharmacodynamics Plant Extracts Analysis Proteins Drug Effects Molecular Structure Pearson's Correlation Coefficient Factor Analysis Regression Prediction Models Tuberculosis, Multidrug-Resistant Drug Therapy Drug Efficacy ab: 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. pubtype: Academic Journal doctype: equations & formulas pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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