Synthesis, Antibacterial, Antibiofilm, and Docking Studies of Chalcones Against Multidrug Resistance Pathogens

Abstract

The escalating threat of drug-resistant microbes underscores the urgent need for novel antimicrobial agents. In response, considerable research effort has been directed towards developing innovative frameworks and strategies to address this challenge. Chalcones, known for their broad-spectrum biological activities, have emerged as promising candidates for combating drug resistance. In this study, a series of 2’-Hydroxychalcones (5a, 5b, 5c, and 5d) with varying electron withdrawing and donating groups were synthesized via Claisen Schmidt condensation. Structural confirmation of synthesized compounds was achieved through FT-IR, 1H NMR, and 13C NMR analyses. Subsequent evaluation of the synthesized compounds revealed their potential as antibacterial and antibiofilm agents. Notably, compounds 5a and 5d exhibited potent antibacterial activity against multidrug-resistant (MDR) bacteria E. coli, P. aeruginosa, K. pneumoniae, and S. aureus, surpassing the reference drug Ciprofloxacin (30 μg/ml) and other synthesized compounds. Compound 5d demonstrated a remarkable zone of inhibition of 19.5 mm against K. pneumoniae. Furthermore, 5a (at a concentration of 30 μg) and 5d (at a concentration of 50 μg) exhibited statistically significant (P > 0.05) biofilm inhibition efficacy compared to Ciprofloxacin (30 μg/ml). The synthesized chalcones 5a-5d were also docked via PachDock molecular docking software for Glucosamine-6-phosphate (GlcN-6-P) synthase inhibition and showed that ligand 5a exhibited outstanding results with score 4,238 and ACE value –160.89 kcal/mol, consistent with the observed antibacterial activity. These findings underscore the potential of chalcones, particularly 5a and 5d, as promising candidates for the development of new antimicrobial agents targeting drug-resistant microbes and biofilm formation.