Abstract
This study explores the synthesis of chlorine-substituted flavanones and their biotechnologically derived glycosides in order to evaluate how structural modifications influence both antimicrobial activity and pharmacokinetic properties, with attention to issues such as solubility and membrane transport. Four chloroflavanones (2'-, 3'-, 4'-, and 6-chloroflavanone) were synthesized and biotransformed using entomopathogenic fungi to obtain glycosylated derivatives. Antimicrobial activity was assessed against five microbial strains, while pharmacokinetic properties were predicted computationally. Results showed that 4'-chloroflavanone demonstrated the strongest antimicrobial activity, particularly against Gram-positive bacteria Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 19433. Most compounds unexpectedly promoted Escherichia coli ATCC 25922 growth, except 4'-chloroflavanone and 3'-chloroflavanone 6-O-β-D-(4″-O-methyl)-glucopyranoside. Nearly all compounds exhibited antifungal activity against Candida albicans ATCC 10231. Glycosylation generally reduced antimicrobial potency but improved water solubility and in silico predictions indicate markedly reduced blood-brain barrier permeation and potential P-glycoprotein recognition. Selective chlorine substitution combined with biotechnological glycosylation may offer a route to antimicrobial flavonoids with improved aqueous solubility and favorable predicted pharmacokinetics.