Enhancing the physicochemical properties and bioactivities of 2'-hydroxyflavanone through fungal biotransformation

Flavonoids comprise a group of natural compounds with diverse bioactivities; however, their low water solubility and limited bioavailability often impede their potential health benefits for humans. In this study, five derivatives, namely 2',5'-dihydroxyflavanone (1), 2'-dihydroxyflavanone-5'-O-4″-O-methyl-β-d-glucoside (2), 2'-dihydroxyflavanone-6-O-4″-O-methyl-β-d-glucoside (3), 2'-dihydroxyflavanone-3'-O-4″-O-methyl-β-d-glucoside (4) and hydroxyflavanone-2'-O-4″-O-methyl-β-d-glucoside (5), were biosynthesized from 2'-hydroxyflavanone through microbial transformation using Beauveria bassiana ATCC 7159. Product 1 was identified as a known compound while 2-5 were structurally characterized as new structures through extensive 1D and 2D NMR analysis. The water solubility of biotransformed products 1-5 was enhanced by 30-280 times compared to the substrate 2'-hydroxyflavanone. Moreover, the antioxidant assay revealed that 1 and 2 exhibited improved 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity relative to the substrate, decreasing the logIC₅₀ from 8.08 ± 0.11 μM to 6.19 ± 0.08 μM and 7.15 ± 0.08 μM, respectively. Compound 5 displayed significantly improved anticancer activity compared to the substrate 2'-hydroxyflavanone against Glioblastoma 33 cancer stem cells, decreasing the IC₅₀ from 25.05 μM to 10.59 μM. Overall, fungal biotransformation represents an effective tool to modify flavonoids for enhanced water solubility and bioactivities.