Isatin-derived azoles as new potential antimicrobial agents: Design, synthesis and biological evaluation

Bioorg Med Chem Lett. 2021 Jun 1:41:128030. doi: 10.1016/j.bmcl.2021.128030. Epub 2021 Apr 8.

Abstract

Novel antibiotics are forced to be developed on account of multidrug-resistant bacteria with serious threats to human health. This work developed isatin-derived azoles as new potential antimicrobial agents. Bioactive assay revealed that isatin hybridized 1,2,4-triazole 7a exhibited excellent inhibitory activity against E. coli ATCC 25,922 with an MIC value of 1 µg/mL, which was 8-fold more potent than reference drug norfloxacin. The active molecule 7a possessed the ability to kill some bacteria and fungi as well as displayed low propensity to induce resistance towards E. coli ATCC25922. Preliminary mechanism investigation indicated that hybrid 7a might block deoxyribonucleic acid (DNA) replication by intercalating with DNA and possibly interacting with DNA polymerase III, thus exerting its antimicrobial potency.

Keywords: Antimicrobial; Azoles; DNA; Isatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Azoles / chemical synthesis
  • Azoles / chemistry
  • Azoles / pharmacology*
  • Bacteria / drug effects*
  • Dose-Response Relationship, Drug
  • Drug Design
  • Fungi / drug effects*
  • Humans
  • Isatin / chemistry
  • Isatin / pharmacology*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Antifungal Agents
  • Azoles
  • Isatin