Synthesis and In Vitro Screening of Methicillin‐Resistant <i>Staphylococcus aureus</i> 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.