Synthesis and In Vitro Screening of Methicillin‐Resistant Staphylococcus aureus Inhibitory Activity of New Bis(benzimidazole‐1,3,4‐oxadiazole) Hybrids Linked by Different Spacers

ABSTRACT The development of novel scaffolds with methicillin‐resistant Staphylococcus aureus (MRSA) inhibitory activity is crucial as a result of antibiotic abuse and the rise in MRSA strains. Starting from 2‐(5‐mercapto‐1,3,4‐oxadiazol‐2‐yl)phenol 4 , we investigated the bacterial inhibitory activity of new bis(benzimidazole‐1,3,4‐oxadiazole) hybrids 1 that are linked by different spacers. The bis‐products 1 displayed a wide spectrum of bacterial inhibitory potency with MIC and MBC in the ranges from 1.1 to 126.9 and 2.4 to 253.8 µM, respectively, against S. aureus , S. mutans , E. faecalis , E. coli , P. aeruginosa , and Klebsiella pneumoniae . The hexane‐linked bis(1‐benzyl‐1 H ‐benzo[ d ]imidazole) 1 h showed significant potency that exceeded ciprofloxacin against S. aureus and E. faecalis with an MIC/MBC of 1.1/2.1 µM. It also had an MIC/MBC of 2.1/4.3 µM against S. mutans , E. coli , and P. aeruginosa . Additionally, 1 h showed interesting MRSA inhibitory potency that exceeded linezolid with an MIC/MBC of 2.1/4.3 µM as well as comparable anti‐biofilm activity to ciprofloxacin with an IC 50 of 4.6 ± 0.12 µM. As indicated by the Ames test, 1 h was not mutagenic to Salmonella typhimurium strains.