Antimicrobial mechanism of action and cytotoxicity of prenylated phenolic compounds.

Prenylated (iso)flavonoids are plant-derived compounds with potent antimicrobial activity. To apply them as novel alternatives to traditional antimicrobial agents, two major aspects that should be well characterized are their mechanism of antimicrobial action and their toxicity. To increase current understanding on their mechanism of antimicrobial action, this project will systematically study their effects on microbial lipid membranes and their potential self-assembly behaviour outside and inside lipid membranes using in vitro and in silico techniques. The cytotoxicity and intestinal absorption of prenylated (iso)flavonoids will be further evaluated using new approach methodologies including in vitro cell-based assays and in silico QSAR models, which provide a mechanistic understanding of the toxic potential of prenylated (iso)flavonoids based on their chemical structure. These processes (effects on lipid membranes, self-assembly, cytotoxicity, and absorption) are influenced by different governing properties of prenylated (iso)flavonoids (e.g. hydrophobicity, charge, flexibility, polar surface areas). Within this project structural analogues of prenylated (iso)flavonoids will be studied systematically, allowing the establishment of (quantitative) structure-activity relationships.