Synthesis, antibacterial, antibiofilm, and docking studies of chalcones against multidrug resistance pathogens

• Published in: Heliyon 2024-07, Vol.10 (13), p.e30618, Article e30618
• Main Authors: Nawaz, Tariq, Tajammal, Affifa, Qurashi, Aisha Waheed, Nisa, Mehr-un, Binjawhar, Dalal Nasser, Iqbal, Munawar
• Format: Article
• Language: English
• Subjects: Antibacterial activity; Antibiofilm activity; Chalcones; GlcN-6-P synthase inhibition
• ISSN: 2405-8440; 2405-8440
• DOI: 10.1016/j.heliyon.2024.e30618

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. FT-IR, 1H NMR, and 13C NMR analyses were employed to confirm the structure of the synthesized compounds. 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 showed a notable 19.5 mm zone of inhibition 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 4238 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.