Investigation of Antimicrobial Activity of Amino Acid- and Triphenylphosphonium-Based Derivatives of Chrysin and Pinocembrin

Objectives: Chrysin and pinocembrin are two key flavonoids contributing to the antimicrobial activity of poplar propolis. However, their antimicrobial potency when used independently is limited. In this study, amino acid (AA)- and triphenylphosphonium (TPP)-based derivatives of chrysin and pinocembrin were designed, synthesised, and evaluated for their antimicrobial activity, with particular focus on their antifungal potential and mechanism of action. Methods: AA- and TPP-based derivatives of chrysin and pinocembrin were synthesised and characterised. Their antimicrobial activity was evaluated against selected bacterial and fungal strains. The mechanism of antifungal activity of the most active compounds was further investigated. Additionally, their haemolytic activity was also evaluated. Results and Conclusions: TPP derivatives, compounds 11 and 12, showed substantially enhanced antimicrobial activity against Candida albicans, Candida glabrata, Candida krusei, Staphylococcus aureus, and Escherichia coli. Further investigation indicated that compounds 11 and 12 are capable of inducing membrane depolarisation while exhibiting negligible haemolytic activity. These findings support TPP-based derivatisation as a promising approach for improving the antimicrobial potential of these propolis-derived flavonoids.