Phenylhydrazone linked 1,2,3-triazole hybrids: synthesis, antimicrobial evaluation and docking studies as dual inhibitors of DNA gyrase and lanosterol 14-alpha demethylase

摘要

In an effort to develop new antimicrobial agents, a novel series of new phenylhydrazone linked triazole hybrids was synthesized via Cu(I)-catalyzed azide alkyne cycloaddition (CuAAC) using the concept of molecular hybridization. In the present era, molecular hybridization is one of the most significant tool to develop novel drug molecules by combining two or more bioactive scaffolds. All synthesized compounds were characterized by using various spectral methods like FTIR, H-1 NMR, C-13 NMR including HRMS data. The antimicrobial evaluation results indicated that all the synthesized phenylhydrazone linked triazole hybrids were more efficacious than phenylhydrazone linked terminal alkynes towards the tested bacterial strains and also showed comparable antifungal potency to standard drug fluconazole. Compound 6e exhibited very good potency against E. coli (MIC = 0.0113 mu mol/mL), P. fluorescens (MIC = 0.0113 mu mol/mL), S. enterica (MIC = 0.0057 mu mol/mL), and C. albicans (MIC = 0.0057 mu mol/mL). The docking simulations of all three alkynes (3a-3c) and their corresponding 1,2,3-triazole hybrids (5b, 6e, 7e and 7b) were also carried out onto E. coli DNA gyrase and C. albicans lanosterol 14-alpha demethylase The docking score of most promising compound 6e with lanosterol 14-alpha demethylase is - 11.6 kcal/mol.