Pyrazoline tethered 1,2,3-triazoles: Synthesis, antimicrobial evaluation and in silico studies

A new series of pyrazoline-amide linked 1,2,3-triazole hybrids was wisely designed and synthesized using 1,3-dipolar cycloaddition between pyrazoline linked alkynes and 2-bromo-N-arylacetamide. All the newly synthesized compounds were evaluated in vitro against different microbial strains viz. Escherichia coli, Bacillius subtilis, Staphylococcus aureus, Aspergillus niger, and Candida albicans. Pyrazoline linked terminal alkynes (4a-c) showed MIC = 0.062-0.078 mu mol/mL against different bacterial and fungal strain. However, pyrazoline-amide linked 1,2,3-triazole hybrids (6a-6t ) showed MIC = 0.0229-0.050 mu mol/mL. Compound 6e exhibited better efficacy against E. coli and both the fungal strains compared to standard drugs used. Docking studies of the most potent compounds were carried out against bacterial DNA Gyr A and fungal 14 alpha-steroldemethylase were also performed. The binding potential of 4a and 6e with both the target using molecular dynamics simulations was also investigated. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

A new series of pyrazoline-amide linked 1,2,3-triazole hybrids were successfully synthesized and showed promising antimicrobial activity, with compound 6e exhibiting superior efficacy. Docking studies and molecular dynamics simulations confirmed the binding potential of compounds 4a and 6e to bacterial and fungal targets.