Synthesis, characterization, biological evaluation and molecular docking study of some novel phenoxy methyl linked 1,2,3-triazole derivatives bridged with amide functionalities via ‘click chemistry’ approach

Abstract

Herein, a new series of phenoxy methyl linked 1,4-disubstituted 1,2,3-triazole derivatives (SR1–SR16) was synthesized by click reaction and copper-catalyzed Huisgen [3 + 2] cycloaddition in the presence of copper sulphate and sodium ascorbate. All the newly synthesized compounds were characterized via Mass, 1H NMR, 13C NMR, FT-IR spectroscopy, and elemental analysis and evaluated for their antimalarial and antimicrobial activities. Among the synthesized compounds, SR12 containing naphthyl substituent is found to be the most active compound with IC50 of 18.60 μM in antimalarial activities and SR7 and SR9 were found to exhibit good antimicrobial activity at 600.83 μM and 614.12 μM concentration respectively. The antimalarial activity of the synthesized compounds was further supplemented by molecular docking studies against the PfDHFR (PDB ID- 3QGT) receptor, revealing that the remarkable binding affinity values and key interactions as compared to the standard reference Chloroquine. The drug-likeness properties of these compounds were supported by predicted pharmacokinetics.