Competitive α-glucosidase inhibitors, dihydrobenzoxanthones, from the barks of <i>Artocarpus elasticus</i>

Abstract

This study aimed to search the α-glucosidase inhibitors from the barks part of <i>Artocarpus elasticus</i>. The responsible compounds for α-glucosidase inhibition were found out as dihydrobenzoxanthones (<b>1</b>-<b>4</b>) and alkylated flavones (<b>5</b>-<b>6</b>). All compounds showed a significant enzyme inhibition toward α-glucosidase with IC₅₀s of 7.6-25.4 μM. Dihydrobenzoxanthones (<b>1</b>-<b>4</b>) 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 <b>1</b> manifested as the competitive and reversible simple slow-binding, with kinetic parameters <i>k</i>₃ = 0.0437 µM^-1min^-1, <i>k</i>₄ = 0.0166 min^-1, and <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msubsup><mml:mrow><mml:mi>K</mml:mi></mml:mrow><mml:mrow><mml:mi>i</mml:mi></mml:mrow><mml:mrow><mml:mi>app</mml:mi></mml:mrow></mml:msubsup></mml:math> = 0.3795 µM. Alkylated flavones (<b>5</b>-<b>6</b>) were mixed type I (<i>K</i>_I < <i>K</i>_IS) inhibitors. The binding affinities (<i>K</i>_SV) represented by all inhibitors were correlated to their concentrations and inhibitory potencies (IC₅₀). Moreover, compounds <b>1</b> and <b>5</b> were identified as new ones named as artoindonesianin W and artoflavone B, respectively. Molecular modelling study proposed the putative binding conformation of competitive inhibitors (<b>1</b>-<b>4</b>) to α-glucosidase at the atomic level.