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

• Published in: Journal of molecular structure 2021-12, Vol.1246, p.131154, Article 131154
• Main Authors: Kumar, Lokesh, Lal, Kashmiri, Kumar, Ashwani, Paul, Avijit Kumar, Kumar, Anil
• Format: Article
• Language: English
• Subjects: Amide; Antimicrobial agent; Crystal structure; Docking studies; Pyrazoline; Triazole
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2021.131154

•New series of pyrazoline-amide linked 1,2,3-triazole hybrids was synthesized.•Pyrazoline-amide linked 1,2,3-triazole hybrid exhibited better antimicrobial activity compared to their precursors.•Docking studies were performed with E. coli Gyr A and A. Niger 14-α-demethylase.•The binding potential of 6e with both the target using molecular dynamics simulations was also studied. 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 μmol/mL against different bacterial and fungal strain. However, pyrazoline-amide linked 1,2,3-triazole hybrids (6a-6t) showed MIC = 0.0229–0.050 μmol/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 14α-steroldemethylase were also performed. The binding potential of 4a and 6e with both the target using molecular dynamics simulations was also investigated. [Display omitted]