Synthesis, Structural Characterization, And Biological Evaluation Of Salicyaldehyde-Derived Fluorinated Chalcones With Enhanced Antimicrobial Activity

A series of novel fluorinated chalcone analogues incorporating a hydroxybenzaldehyde framework was successfully synthesized and systematically investigated. The synthetic approach involved a base-catalyzed Claisen–Schmidt condensation between various hydroxy-substituted benzaldehydes and fluorinated acetophenone derivatives. The structures of the synthesized compounds were unequivocally established using detailed spectroscopic techniques, including ^1H NMR, ^13C NMR, infrared spectroscopy, and mass spectrometry. The antimicrobial activity of the prepared chalcone derivatives was evaluated against a panel of clinically relevant bacterial and fungal strains, including Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans. Several compounds demonstrated significant antimicrobial potency, with minimum inhibitory concentration (MIC) values ranging from 5 to 25 μg/mL. Structure–activity relationship (SAR) studies revealed that the antimicrobial efficacy is strongly influenced by the number and positional arrangement of hydroxyl groups, as well as the electronic effects imparted by fluorine substitution within the chalcone scaffold. In conclusion, the study highlights the potential of fluorinated hydroxychalcone derivatives as promising antimicrobial candidates and provides important insights for the rational design and development of more potent next-generation antimicrobial agents.