Synthesis of a tetralone derivative of ampicillin to control ampicillin-resistant Staphylococcusaureus.

Sourav Chakraborty, Piyush Baindara, Suresh K Mondal, Dinata Roy, Santi M Mandal

Biochemical and biophysical research communications 2024 Jun 25

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Due to the rapid emergence of antibiotic resistant new bacterial strains and new infections, there is an urgent need for novel or newly modified and efficient alternatives of treatment. However, conventional antibiotics are still used in therapeutic settings but their efficacy is uncertain due to the rapid evolution of drug resistance. In the present study, we have synthesized a new derivative of conventional antibiotic ampicillin using SN2-type substitution reaction. NMR and mass analysis of the newly synthesized derivative of ampicillin confirmed it as ampicillin-bromo-methoxy-tetralone (ABMT). Importantly, ABMT is revealed to have efficient activity against Staphylococcus aureus (S. aureus) with a MIC value of 32 μg ml-1 while ampicillin was not effective, even at 64 μg ml-1 of concentration. Electron microscopy results confirmed the membrane-specific killing of S. aureus at 1 h of treatment. Additionally, molecular docking analysis revealed a strong binding affinity of ABMT with β-lactamase via the formation of a closed compact bridge. Our findings, avail a new derivative of ampicillin that could be a potential alternative to fight ampicillin-resistant bacteria possibly by neutralizing the β-lactamase action. Copyright © 2024 Elsevier Inc. All rights reserved.

Citation

Sourav Chakraborty, Piyush Baindara, Suresh K Mondal, Dinata Roy, Santi M Mandal. Synthesis of a tetralone derivative of ampicillin to control ampicillin-resistant Staphylococcusaureus. Biochemical and biophysical research communications. 2024 Jun 25;714:149974