Rational Design, Synthesis, and in silico Bio-efficacy of Triazole-Clubbed Chalcone Hybrids

Abstract This study reports an effective intramolecular cycloaddition of N-tosylhydrazones with 4-aminoacetophenone, facilitated by I2/DMSO, and thus forming acetylated 1,4-disubstituted 1,2,3-triazoles. This method provides a straightforward, versatile, and efficient approach for synthesizing 1,4-disubstituted 1,2,3-triazoles under metal- and azide-free conditions, utilizing molecular iodine. Furthermore, functionalization was carried out to obtain 1,2,3-triazole-clubbed-chalcone hybrids, and these compounds were subsequently tested for their in silico antimicrobial activity, considering the known potential bioactivities of these two pharmacophores. In silico molecular docking studies revealed that nearly all the compounds exhibited better docking scores than the standard drug ciprofloxacin against both S. aureus (PDB ID:3G75) and E. coli (PDB ID:1GRX). Among these, compound 5e showed the most favorable docking score of −8.3 ± 0.46 kcal/mol for S. aureus, and compound 5t showed the best docking score of −8.2 ± 0.78 kcal/mol for E. coli. Compound 5i showed a better docking score compared to the antifungal drug fluconazole for A. niger (PDB ID:1WS3), with a docking score of −9.5 ± 0.72 kcal/mol. The results of these experimental findings underscore the potential of these 1,2,3-triazole-clubbed chalcone hybrids to function as effective multifunctional agents with antibacterial and antifungal capabilities.