Synthesis of novel quinoline-based thiadiazole, evaluation of their antileishmanial potential and molecular docking studies

Bioorg Chem. 2019 Apr:85:109-116. doi: 10.1016/j.bioorg.2018.12.025. Epub 2018 Dec 21.

Abstract

New series of quinoline-based thiadiazole analogs (1-20) were synthesized, characterized by EI-MS, 1H NMR and 13C NMR. All synthesized compounds were subjected to their antileishmanial potential. Sixteen analogs 1-10, 12, 13, 16, 17, 18 and 19 with IC50 values in the range of 0.04 ± 0.01 to 5.60 ± 0.21 µM showed tremendously potent inhibition as compared to the standard pentamidine with IC50 value 7.02 ± 0.09 µM. Analogs 11, 14, 15 and 20 with IC50 8.20 ± 0.35, 9.20 ± 0.40, 7.20 ± 0.20 and 9.60 ± 0.40 µM respectively showed good inhibition when compared with the standard. Structure-activity relationships have been also established for all compounds. Molecular docking studies were performed to determine the binding interaction of the compounds with the active site target.

Keywords: Antileishmanial; Molecular docking studies; Quinoline; SAR; Synthesis; Thiadiazole.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalytic Domain
  • Leishmania donovani / chemistry
  • Leishmania major / drug effects
  • Microbial Sensitivity Tests
  • Molecular Docking Simulation
  • Molecular Structure
  • Oxidoreductases / chemistry
  • Oxidoreductases / metabolism
  • Protein Binding
  • Quinolines / chemical synthesis
  • Quinolines / metabolism
  • Quinolines / pharmacology*
  • Structure-Activity Relationship
  • Thiadiazoles / chemical synthesis
  • Thiadiazoles / metabolism
  • Thiadiazoles / pharmacology*
  • Trypanocidal Agents / chemical synthesis
  • Trypanocidal Agents / metabolism
  • Trypanocidal Agents / pharmacology*

Substances

  • Quinolines
  • Thiadiazoles
  • Trypanocidal Agents
  • Oxidoreductases
  • pteridine reductase