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

Bioorg Med Chem Lett. 2021 Mar 25:127995. doi: 10.1016/j.bmcl.2021.127995. Online ahead of print.


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 derivative8b (MIC = 1 μg/mL) was more active than norfloxacin against drug resistant MRSA. Compound8bwas able to disturb the membrane effectively and intercalate into deoxyribonucleic acid (DNA) to form a steady8b-DNA complex, which might be responsible for bacterial metabolic inactivation. Molecular docking indicated that8bcould 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 derivative8bdeserved further investigation as a new lead compound.

PMID:33775834 | DOI:10.1016/j.bmcl.2021.127995