1,2,4-Triazole and 1,3,4-oxadiazole analogues: Synthesis, MO studies, in silico molecular docking studies, antimalarial as DHFR inhibitor and antimicrobial activities

Bioorg Med Chem. 2017 Aug 1;25(15):4064-4075. doi: 10.1016/j.bmc.2017.05.054. Epub 2017 May 27.

Abstract

1,2,4-Triazole and 1,3,4-oxadiazole analogues are of interest due to their potential activity against microbial and malarial infections. In search of suitable antimicrobial and antimalarial compounds, we report here the synthesis, characterization and biological activities of 1,2,4-triazole and 1,3,4-oxadiazole analogues (SS 1-SS 10). The molecules were characterized by IR, mass, 1H NMR, 13C NMR and elemental analysis. The in vitro antimicrobial activity was investigated against pathogenic strains, the results were explained with the help of DFT and PM6 molecular orbital calculations. In vitro cytotoxicity and genotoxicity of the molecules were studied against S. pombe cells. In vitro antimalarial activity was studied. The active compounds were further evaluated for enzyme inhibition efficacy against the receptor Pf-DHFR computationally as well as in vitro to prove their candidature as lead dihydrofolate reductase inhibitors.

Keywords: 1,2,4-Triazole; 1,3,4-Oxadiazole; Anti-malarial activity; Anti-microbial activity; DFT; DHFR; Molecular docking; PM6; S. pombe.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Infective Agents / pharmacology*
  • Antimalarials / pharmacology*
  • Folic Acid Antagonists / pharmacology*
  • Molecular Docking Simulation
  • Oxadiazoles / chemistry*
  • Oxadiazoles / pharmacology
  • Spectrum Analysis / methods
  • Triazoles / chemistry*
  • Triazoles / pharmacology

Substances

  • Anti-Infective Agents
  • Antimalarials
  • Folic Acid Antagonists
  • Oxadiazoles
  • Triazoles
  • 1,3,4-oxadiazole
  • 1,2,4-triazole