Competitive α-glucosidase inhibitors, dihydrobenzoxanthones, from the barks of Artocarpus elasticus

Abstract

This study aimed to search the α-glucosidase inhibitors from the barks part of Artocarpus elasticus. The responsible compounds for α-glucosidase inhibition were found out as dihydrobenzoxanthones (1-4) and alkylated flavones (5-6). All compounds showed a significant enzyme inhibition toward α-glucosidase with IC₅₀s of 7.6-25.4 μM. Dihydrobenzoxanthones (1-4) exhibited a competitive inhibition to α-glucosidase. This competitive behaviour was fully characterised by double reciprocal plots, Yang's method, and time-dependent experiments. The compound 1 manifested as the competitive and reversible simple slow-binding, with kinetic parameters k₃ = 0.0437 µM^-1 min^-1, k₄ = 0.0166 min^-1, and $K_i^{\mathrm{app}}$ = 0.3795 µM. Alkylated flavones (5-6) were mixed type I (K_I < K_IS) inhibitors. The binding affinities (K_SV) represented by all inhibitors were correlated to their concentrations and inhibitory potencies (IC₅₀). Moreover, compounds 1 and 5 were identified as new ones named as artoindonesianin W and artoflavone B, respectively. Molecular modelling study proposed the putative binding conformation of competitive inhibitors (1-4) to α-glucosidase at the atomic level.

Keywords: artoflavone B and α-glucosidase inhibition; artoindonesianin W; dihydrobenzoxanthones.