Fungal biotransformation of 2′-methylflavanone and 2′-methylflavone as a method to obtain glycosylated derivatives

Abstract

Methylated flavonoids are promising pharmaceutical agents due to their improved metabolic stability and increased activity compared to unmethylated forms. The biotransformation in cultures of entomopathogenic filamentous fungi is a valuable method to obtain glycosylated flavones and flavanones with increased aqueous solubility and bioavailability. In the present study, we combined chemical synthesis and biotransformation to obtain methylated and glycosylated flavonoid deriva-tives. In the first step, we synthesized 2′-methylflavanone and 2′-methylflavone. Afterwards, both compounds were biotransformed in the cultures of two strains of entomopathogenic filamentous fungi Beauveria bassiana KCH J1.5 and Isaria fumosorosea KCH J2. We determined the structures of biotransfor-mation products based on NMR spectroscopy. Biotransformations of 2′-methyflavanone in the culture of B. bassiana KCH J1.5 resulted in three glycosylated flavanones: 2′-methylflavanone 6-O-β-D-(4′′-O-methyl)-glucopyranoside, 3′-hydroxy-2′-methylflavanone 6-O-β-D-(4′′-O-methyl)-glucopyranoside, and 2-(2′-methylphenyl)-chromane 4-O-β-D-(4′′-O-methyl)-glucopyranoside, whereas in the culture of I. fumosorosea KCH J2, two other products were obtained: 2′-methylflavanone 3′-O-β-D-(4′′-O-methyl)-glucopyranoside and 2-methylbenzoic acid 4-O-β-D-(4′-O-methyl)-glucopyranoside. 2′-Methylflavone was effectively biotransformed only by I. fumosorosea KCH J2 into three derivatives: 2′-methylflavone 3′-O-β-D-(4′′-O-methyl)-glucopyranoside, 2′-methylflavone 4′-O-β-D-(4′′-O-methyl)-glucopyranoside, and 2′-methylflavone 5′-O-β-D-(4′′-O-methyl)-glucopyranoside. All obtained glycosylated flavonoids have not been described in the literature until now and need further research on their biological activity and pharmacological efficacy as potential drugs.