Divergent Synthesis, Antibacterial and Antibiofilm Evaluation, and In Silico ADMET Analysis of Hydroxy Flavanones, Flavones, Aurones, and O-Propynyloxy Aurones

Abstract

Bacterial biofilms cause chronic infections by resisting the effectiveness of existing antibiotics. Staphylococcus aureus is a readily biofilm-forming pathogen that may cause severe health issues through its survival in indwelling medical devices. Salmonella enterica causes prevalent food poisoning and affects millions of people globally. Our study focused on the antibacterial, antibiofilm activities, and pharmacokinetic properties of the chemically synthesized flavonoids. A simple and effective protocol for synthesizing flavanones, flavones, O-propynyloxy aurones, and hydroxy aurones from O-propynyloxy chalcones was established. All the flavonoids except a few showed good zones of inhibition against both the above-mentioned bacterial pathogens. Flavonoids showed more than 50% inhibition in all the tested antibiofilm activities. Confocal images gave clear visual evidence for the decrease in cell density of the biofilms after flavonoids treatment. Among the synthesized compounds, compound 9h exhibited the highest antibacterial activity against S. aureus, while compound 8g was most effective against S. enterica. In terms of antibiofilm activity, compound 8g showed the strongest inhibition against S. aureus, whereas compound 10a demonstrated the highest activity against S. enterica. Pharmacokinetic studies suggest that these flavonoids, with appropriate structural modifications, could serve as promising candidates for the development of orally administrable agents targeting bacterial pathogens.