Synthesis, characterization, and biological evaluation of hydroxybenzaldehyde derivatives of fluorinated chalcones with enhanced antimicrobial activity

Abstract

A library of previously unreported fluorinated chalcone analogues incorporating a hydroxybenzaldehyde scaffold was successfully synthesized and systematically characterized. The synthetic strategy was based on a base-catalyzed Claisen-Schmidt condensation between differently hydroxy-substituted benzaldehydes and fluorinated acetophenone derivatives. Structural confirmation of the obtained compounds was achieved through comprehensive spectroscopic analysis, including 1H NMR, 13C NMR, infrared spectroscopy, and mass spectrometry. The antimicrobial potential of the synthesized chalcones was assessed against a set of clinically significant bacterial and fungal pathogens, namely Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans. Several compounds exhibited pronounced antimicrobial activity, as evidenced by minimum inhibitory concentration (MIC) values in the range of 5-25 ?g/mL. Structure-activity relationship (SAR) analysis indicated that both the number and positional orientation of hydroxyl substituents, along with the electronic influence of fluorine atoms, play a decisive role in governing the antimicrobial performance of the chalcone framework. Overall, the findings underscore the therapeutic promise of fluorinated hydroxychalcone derivatives as effective antimicrobial leads and offer valuable insights for the rational development of next-generation antimicrobial agents.