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Molecular docking simulation, drug-likeness assessment, and pharmacokinetic study of some cephalosporin analogues against a penicillin-binding protein of Salmonella typhimurium


In pursuit of novel antibiotics that could curb the growing trend of multidrug resistance by Salmonella typhimurium, a data set of some cephalosporin analogues were subjected to Molecular Docking based virtual screening against a penicillin-binding protein (PBP 1b) of the bacterium to ascertain the binding affinity values of the bioactive ligands against the active sites of the PBP 1b protein target using the AutoDock Vina Software. Three compounds with binding affinity values ranging from −7.8 kcal/mol to −8.2 kcal/mol were selected as the most promising leads. The selected compounds also displayed better potencies against the bacterium when compared with Cefuroxime (binding affinity = −6.4 kcal/mol), a standard β-lactam antibiotic used herein for quality control and assurance. Furthermore, evaluation of the drug-likeness and ADMET properties of the three most promising leads revealed that they possess good oral bioavailability and excellent pharmacokinetic profiles. It is hoped that the findings of this study will provide an excellent template for developing more potent β-lactam antibiotics against Salmonella typhimurium.

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We appreciate the technical support of the staff and Postgraduate students of the Physical Chemistry Unit of Ahmadu Bello University Zaria, Nigeria.

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The research was designed by AU, and supervised by AGS and SU. JPA carried out the computational analysis and drafted the manuscript.

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Correspondence to Philip John Ameji.

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Ameji, P.J., Uzairu, A., Shallangwa, G.A. et al. Molecular docking simulation, drug-likeness assessment, and pharmacokinetic study of some cephalosporin analogues against a penicillin-binding protein of Salmonella typhimurium. J Antibiot 76, 211–224 (2023).

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