Abstract
Staphylococcusaureus is an important opportunistic pathogen that causes many infections in humans and animals. The inappropriate use of antibiotics has favored the diffusion of methicillin-resistant S. aureus (MRSA), nullifying the efforts undertaken in the discovery of antimicrobial agents. Oxadiazole heterocycles represent privileged scaffolds for the development of new drugs because of their unique bioisosteric properties, easy synthesis, and therapeutic potential. A vast number of oxadiazole-containing derivatives have been discovered as potent antibacterial agents against multidrug-resistant MRSA strains. Here, we investigate the ability of a new library of oxadiazoles to contrast the growth of Gram-positive and Gram-negative strains. The strongest antimicrobial activity was obtained with compounds 3 (4 µM) and 12 (2 µM). Compound 12, selected for further evaluation, was found to be noncytotoxic on the HaCaT cell line up to 25 µM, bactericidal, and was able to improve the activity of oxacillin against the MRSA. The highest synergistic interaction was obtained with the combination values of 0.78 μM for compound 12, and 0.06 μg/mL for oxacillin. The FIC index value of 0.396 confirms the synergistic effect of compound 12 and oxacillin. MRSA treatment with compound 12 reduced the expression of genes included in the mec operon. In conclusion, 12 inhibited the growth of the MRSA and restored the activity of oxacillin, thus resulting in a promising compound in the treatment of MRSA infection.
Highlights
Antibiotics are a class of drugs traditionally used as the first strategy against serious infections caused by bacteria
The inappropriate use of antibiotics has favored the diffusion of methicillinresistant S. aureus (MRSA), nullifying the efforts undertaken in the discovery of antimicrobial agents
This is the case with β-lactams and the selection of methicillin-resistant S. aureus (MRSA), which has nullified the efforts undertaken in the discovery of antimicrobial agents [3]
Summary
Antibiotics are a class of drugs traditionally used as the first strategy (weapon) against serious infections caused by bacteria. Antibiotics have generally shown efficacy in the treatment of bacterial infections, but their inappropriate and indiscriminate use has favored the diffusion of resistant bacteria. This is the case with β-lactams and the selection of methicillin-resistant S. aureus (MRSA), which has nullified the efforts undertaken in the discovery of antimicrobial agents [3]. S. aureus can form biofilm on medical devices, and this represents a further complication in the management of infections because of the difficulties of antibiotics to penetrate the biofilm layer [4] For all these reasons, S. aureus is considered one of the major causes of hospital-acquired infections worldwide [5]
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