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Methicillin-Resistant Staphylococcus aureus cause many nosocomial, and community-acquired infections, burdening healthcare systems globally. The aim of the current study was to identify the potent inhibitors of MRSA strains as first step towards drug discovery against MRSA related infections. Clioquinol derivatives 1–10 were evaluated against MRSA strains, using microplate alamar blue assay (MABA). Among them compounds 1–3, and 6–8 were found to be active with MIC values within the range of 61.08–213.58 µM. Compounds 1, and 7 were found highly potent with MIC values of 64.04 and 61.08 µM, respectively. Both these compounds also showed interactions with key residues of topoisomerase IV enzyme via non-covalent interactions. Mechanisms of action of the most active compounds 1, and 7 were further studied through AFM, and fluorescence microscopy. It was observed that compounds 1, and 7 caused massive destruction in shape, and greatly reduced the size, and number of viable cells. Flow cytometry analysis showed a significant rise in DiBAC4(3) fluorescence with non-significant rise in PI fluorescence. These compounds showed increased bacterial membrane depolarizatio. Most importantly it was found that compounds 1 and 7 did not cause any hemolytic effect. Moreover, all the compounds were found to be non-cytotoxic against BJ (Human fibroblast) normal cell line. Our findings suggest that compounds 1, and 7 possess highly potent antibacterial activity against three MDR, and one sensitive strains of S. aureus. These compounds could be used as potential antibacterial agents.
Hamid et al. (Sat,) studied this question.