Design and synthesis of new indanol-1,2,3-triazole derivatives as potent antitubercular and antimicrobial agents

Bioorg Med Chem Lett. 2020 Nov 15;30(22):127579. doi: 10.1016/j.bmcl.2020.127579. Epub 2020 Sep 25.

Abstract

In a search of new antitubercular agents, herein we have reported a series of new thirty-two indanol-1,2,3-triazole derivatives. The synthesized compounds were screened for their in vitro antitubercular and antimicrobial activities. Among the screened compounds, most of the compounds have displayed good antitubercular activity against Mycobacterium tuberculosis H37Rv. The compound 5g has been identified as potent antitubercular agent with MIC value 1.56 µM. The most active compounds of the series were further studied for their cytotoxicity against HEK 293 cells using MTT assay and found to be nontoxic. In addition, ten compounds were shown good antimicrobial activities against both antibacterial and antifungal pathogens. A molecular docking study against Mycobacterial enoyl-ACP-reductase (InhA) was performed to gain an insight into the molecular mechanism of antitubercular action. The pharmacokinetic parameters of these compounds were studied and displayed acceptable drug-likeness score.

Keywords: 1,2,3-Triazoles; ADME prediction; Antimicrobial activity; Antitubercular activity; Click chemistry; Molecular docking study.

MeSH terms

  • Antitubercular Agents / chemical synthesis
  • Antitubercular Agents / chemistry
  • Antitubercular Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Design*
  • HEK293 Cells
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Mycobacterium tuberculosis / drug effects*
  • Structure-Activity Relationship
  • Triazoles / chemical synthesis
  • Triazoles / chemistry
  • Triazoles / pharmacology*

Substances

  • Antitubercular Agents
  • Triazoles