Unique para-aminobenzenesulfonyl oxadiazoles as novel structural potential membrane active antibacterial agents towards drug-resistant methicillin resistant Staphylococcus aureus

A class of structurally unique para-aminobenzenesulfonyl oxadiazoles as new potential antimicrobial agents was designed and synthesized from acetanilide. Some target para-aminobenzenesulfonyl oxadiazoles showed antibacterial potency. Noticeably, hexyl derivative 8b (MIC = 1 ?g/mL) was more active than norfloxacin against drug resistant MRSA. Compound 8b was able to disturb the membrane effectively and intercalate into deoxyribonucleic acid (DNA) to form a steady 8b-DNA complex, which might be responsible for bacterial metabolic inactivation. Molecular docking indicated that 8b could interact with DNA topoisomerase IV through noncovalent interactions to form a supramolecular complex and hinder the function of this enzyme. These results indicated that hexyl derivative 8b deserved further investigation as a new lead compound.

Automated summary

A class of structurally unique para-aminobenzenesulfonyl oxadiazoles were designed and synthesized as potential antimicrobial agents, with notable antibacterial potency exhibited by hexyl derivative 8b. Compound 8b could effectively disrupt the membrane and form a steady 8b-DNA complex to potentially cause bacterial metabolic inactivation. Molecular docking revealed that 8b could interact with DNA topoisomerase IV via noncovalent interactions to hinder enzyme function. Hexyl derivative 8b shows promise as a new lead compound for further investigation.