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

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⁻¹min⁻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.