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

Abstract

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.