Please use this identifier to cite or link to this item: http://localhost:8080/xmlui/handle/123456789/7738
Title: Molecular docking-based virtual screening, drug-likeness, and pharmacokinetic profiling of some anti-Salmonella typhimurium cephalosporin derivatives
Authors: Ameji, Philip John
Uzairu, Adamu
Shallangwa, Gideon Adamu
Uba, Sani
Keywords: b-lactam
Antibiotics
Cephalosporin
PBP1a
Salmonella typhimurium
Issue Date: 2023
Publisher: Journal of Taibah University Medical Sciences
Series/Report no.: Original Article;1417-1431
Abstract: Objective: The rising cases of resistance to existing antibiotic therapies in Salmonella typhimurium has made it necessary to search for novel drug candidates. The present study employed the molecular docking technique to screen a set of antibacterial cephalosporin analogues against penicillin-binding protein 1a (PBP1a) of the bacterium. This is the first study to screen cephalosporin analogues against PBP1a, a protein central to peptidoglycan synthesis in S. typhimurium. Methods: Some cephalosporin analogues were retrieved from a drug repository. The structures of the molecules were optimized using the semi-empirical method of Spartan 14 software and were subsequently docked against the active sites of PBP1a using AutoDock vina software. The most potent ligands were chosen as the most promising leads and subsequently subjected to absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling using the SwissADME online server and DataWarrior chemoinformatics program. The CABSflex 2.0 server was used to carry out molecular dynamics (MD) simulation on the most stable ligand eprotein complex. Results: Compounds 3, 23, and 28 with binding affinity (DG) values of 9.2, 8.7, and 8.9 kcal/mol, respectively, were selected as the most promising leads. The ligands bound to the active sites of PBP1a via hydrophobic bonds, hydrogen bonds, and electrostatic interactions. Furthermore, ADMET analyses of the ligands revealed that they exhibited sound pharmacokinetic and toxicity profiles. In addition, an MD study revealed that the most active ligand bound favorably and dynamically to the target protein. Conclusion: The findings of this research could provide an excellent platform for the discovery and rational design of novel antibiotics against S. typhimurium. Additional in vitro and in vivo studies should be carried out on the drug candidates to validate the findings of this study.
URI: http://localhost:8080/xmlui/handle/123456789/7738
ISSN: 1658-3612
Appears in Collections:Vol 18 No 6 (2023)

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