Antimicrobial activity of new glycoside derivatives of chloroflavones obtained by fungal biotransformation

Chlorinated flavonoids represent a unique subclass of flavonoids with chlorine substituents. The incorporation of chlorine atoms and glucosyl moieties may influence their bioavailability, bioactivity, and pharmacological potential. In this study, 2'-chloroflavone, 3'-chloroflavone, 4'-chloroflavone, and 6-chloroflavone were synthesized and biotransformed using entomopathogenic fungi cultures (Isaria fumosorosea KCH J2 and Beauveria bassiana KCH J1.5) to obtain novel glycosylated derivatives. Pharmacokinetic properties and drug-likeness were predicted using cheminformatics tools. Antimicrobial activity was evaluated against several microbial strains. Enterococcus faecalis ATCC 19433 showed complete growth inhibition with 4'-chloroflavone and 6-chloroflavone, while 2'-chloroflavone and 3'-chloroflavone significantly inhibited its growth. Flavonoid glycosides and flavone demonstrated lower efficacy. Staphylococcus aureus ATCC 29213 was completely or strongly inhibited by all tested compounds. Lactobacillus acidophilus ATCC 4356 was moderately inhibited by flavonoid aglycones and slightly inhibited by glycosides. Escherichia coli ATCC 25922 was most effectively inhibited by 4'-chloroflavone and 6-chloroflavone, followed by 2'-chloroflavone and 3'-chloroflavone, with flavone and glycosides showing lower activity. Candida albicans ATCC 1023 exhibited high sensitivity to all compounds. Overall, chlorinated flavones demonstrated greater antimicrobial activity than non-chlorinated counterparts, with aglycones being more effective than glycosylated derivatives. The position of the chlorine atom significantly influences antimicrobial activity.