Potent α-glucosidase inhibitory activity of inoscavin A from fruiting bodies of Fulvifomes fastuosus: Mechanism of action, molecular docking and ADMET

Abstract

The DPPH radical scavenging, α-glucosidase inhibitory, nitric oxide (NO) inhibitory, and cytotoxic activities of the extracts from fruiting bodies of wood-rot basidiomycete Fulvifomes fastuosus were evaluated in this study. While the CH₂Cl₂ extract was biologically inactive, chromatographic fractionation led to the isolation of two chlorinated hydroquinone derivatives, drosophilin A methyl ether (DAME; 1) and drosophilin A (DA; 2). The EtOAc-partitioned fraction, obtained from the partitioning of the MeOH extract, exhibited strong α-glucosidase and NO inhibitory activities. Further investigation led to the isolation of inoscavin A (3) as the major constituent, along with inoscavin E (4) and polyphenols (5–7). Inoscavin A demonstrated potent α-glucosidase inhibition (IC₅₀ = 3.22 µM), surpassing acarbose by 59-fold, and exhibited non-competitive inhibition kinetics (Kᵢ = 3.25 µM). Molecular docking studies supported an allosteric binding mode. It also displayed favorable drug-likeness and ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiles, including good solubility, high intestinal absorption, low central nervous system (CNS) penetration, and absence of hepatotoxicity. These results suggest that F. fastuosus is a promising source of antidiabetic agents, with inoscavin A as a principle active compound.