Synthesis of 1,2,4-triazolo[1,5-a]pyrimidine derivatives: Antimicrobial activity, DNA Gyrase inhibition and molecular docking

Bioorg Chem. 2020 Jan:94:103411. doi: 10.1016/j.bioorg.2019.103411. Epub 2019 Nov 4.

Abstract

A series of 1,2,4-triazolo[1,5-a]pyrimidine derivatives was designed, synthesized and screened for their antibacterial and antifungal activities as well as their safety profile. Compounds 2b, 3a, 6b, 8b, 8c, 8h, 9a,b, 10b, 11a,b and 12a,b showed high activity against Gram-positive and Gram-negative bacteria with MIC values ranging from 0.25 to 2.0 µg/mL. Many compounds were safe with no cytotoxicity against human embryonic kidney and red blood cells at concentration up to 32 µg/mL. Moreover, compound 9a showed the highest inhibitory activity against DNA Gyrase with IC50 = 0.68 µM compared to ciprofloxacin IC50 = 0.85 µM. Molecular docking at DNA Gyrase active site revealed binding mode and docking scores comparable to that of ciprofloxacin confirming their antibacterial activity via DNA Gyrase inhibition.

Keywords: 1,2,4-Triazolo[1,5-a]pyrimidine; Antibacterial; Antifungal; DNA Gyrase inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use*
  • Humans
  • Molecular Docking Simulation / methods*
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / chemistry*
  • Topoisomerase II Inhibitors / pharmacology
  • Topoisomerase II Inhibitors / therapeutic use*

Substances

  • Anti-Bacterial Agents
  • Pyrimidines
  • Topoisomerase II Inhibitors