In silico exploration of 4(α-l-rhamnosyloxy)-benzyl isothiocyanate: A promising phytochemical-based drug discovery approach for combating multi-drug resistant Staphylococcus aureus.

Autor: Bhattacharya S; Department of Agroecology and Crop Production, Faculty of Agrobiology, Food and Natural Resources, Czech University of Life Sciences Prague, Kamýcká 129, Prague 6, Suchdol, 165 00, Czech Republic., Dutta A; Department of Crop Sciences and Agroforestry, Faculty of Tropical AgriSciences, Czech University of Life Sciences Prague, Kamýcká 129, Suchdol, 165 00, Prague 6, Czech Republic., Khanra PK; Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, 39, Assam, India., Gupta N; Department of Crop Sciences and Agroforestry, Faculty of Tropical AgriSciences, Czech University of Life Sciences Prague, Kamýcká 129, Suchdol, 165 00, Prague 6, Czech Republic., Dutta R; Environmental Biotechnology & Genomics Division, CSIR-National Environmental Engineering Research Institute (CSIR-NEERI), Nehru Marg, Nagpur, 440020, India., Tzvetkov NT; Department of Biochemical Pharmacology & Drug Design, Institute of Molecular Biology 'Roumen Tsanev', Bulgarian Academy of Sciences (BAS), Acad. G. Bonchev Str., Bl. 21, 1113, Sofia, Bulgaria., Milella L; Department of Science, University of Basilicata, Via Dell'Ateneo Lucano 10, 85100, Potenza, Italy. Electronic address: luigi.milella@unibas.it., Ponticelli M; Department of Biochemical Pharmacology & Drug Design, Institute of Molecular Biology 'Roumen Tsanev', Bulgarian Academy of Sciences (BAS), Acad. G. Bonchev Str., Bl. 21, 1113, Sofia, Bulgaria; Department of Science, University of Basilicata, Via Dell'Ateneo Lucano 10, 85100, Potenza, Italy.
Jazyk: angličtina
Zdroj: Computers in biology and medicine [Comput Biol Med] 2024 Sep; Vol. 179, pp. 108907. Date of Electronic Publication: 2024 Jul 20.
DOI: 10.1016/j.compbiomed.2024.108907
Abstrakt: Multidrug-resistant (MDR) Staphylococcus aureus infections significantly threaten global health. With rising resistance to current antibiotics and limited solutions, the urgent discovery of new, effective, and affordable antibacterials with low toxicity is imperative to combat diverse MDR S. aureus strains. Hence, in this study, we introduce an in silico phytochemical-based approach for discovering novel antibacterial agents, underscoring the potential of computational approaches in therapeutic discovery. Glucomoringin Isothiocyanate (GMG-ITC) from Moringa oleifera Lam. is one of the phytochemical compounds with several biological activities, including antimicrobial, anti-inflammatory, and antioxidant activities, and is also effective against S. aureus. This study focuses on screening GMG-ITC as a potential drug candidate to combat MDR S. aureus infections through a molecular docking approach. Moreover, interaction amino acid analysis, in silico pharmacokinetics, compound target prediction, pathway enrichment analysis and molecular dynamics (MD) simulations were conducted for further investigation. Molecular docking and interaction analysis showed strong binding affinity towards S. aureus lipase, dihydrofolate reductase, and other MDR S. aureus proteins, including penicillin-binding protein 2a, MepR, D-Ala:D-Ala ligase, and RPP TetM, through hydrophilic and hydrophobic interactions. GMG-ITC also showed a strong binding affinity to cyclooxygenase-2 and FAD-dependent NAD(P)H oxidase, suggesting that it is a potential anti-inflammatory and antioxidant candidate that may eliminate inflammation and oxidative stress associated with S. aureus infections. MD simulations validated the stability of the GMG-ITC molecular interactions determined by molecular docking. In silico pharmacokinetic analysis highlights its potency as a drug candidate, showing strong absorption, distribution, and excretion properties in combination with low toxicity. It acts as an active protease and enzyme inhibitor with moderate activity against GPCR ligands, ion channels, nuclear receptor ligands, and kinases. Enrichment analysis further elucidated its involvement in important biological, molecular, and cellular functions with potential therapeutic applications in diseases like cancer, hepatitis B, and influenza. Results suggest that GMG-ITC is an effective antibacterial agent that could treat MDR S. aureus-associated infections.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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