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

Bioorg Med Chem Lett. 2021 Jun 1:41:127995. doi: 10.1016/j.bmcl.2021.127995. Epub 2021 Mar 26.

Abstract

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 μg/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.

Keywords: Antibacterial; Benzenesulfonyl; DNA; Drug resistance; Oxadiazole.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Oxadiazoles / chemical synthesis
  • Oxadiazoles / chemistry
  • Oxadiazoles / pharmacology*
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Oxadiazoles