Inhibition of α-glucosidase as well as non-enzymatic glycation is thought as an effective method for treating type-2 diabetes mellitus. In this study, we investigated the inhibitory potential and mechanism of 4-hexylresorcinol against α-glucosidase and non-enzymatic glycation by using multispectroscopic analyses and molecular docking. The results of enzyme kinetics showed that 4-hexylresorcinol reversibly inhibited α-glucosidase activity in a noncompetitive way. Fluorescence quenching then revealed that it increased the hydrophobicity of α-glucosidase and changed the conformation of the enzyme by forming the α-glucosidase–hexylresorcinol complex. Thermodynamic analysis and molecular docking further demonstrated that the inhibition of 4-hexylresorcinol on the α-glucosidase was mainly dependent on hydrogen bond and hydrophobic interaction. Moreover, the 4-hexylresorcinol moderately inhibited the formation of fructosamine, and strongly suppressed the generation of α-dicarbonyl compounds and advanced glycation end products (AGEs). The interaction between 4-hexylresorcinol and bovine serum albumin was mainly driven by hydrophobic interaction. This study showed a novel inhibitor of α-glucosidase as well as non-enzymatic glycation, and provided a drug candidate for the prevention and treatment of type-2 diabetes.

抑制α-葡萄糖苷酶以及非酶糖基化被认为是治疗2型糖尿病的有效方法。在这项研究中，我们通过多光谱分析和分子对接研究了4-己基间苯二酚对α-葡萄糖苷酶和非酶糖基化的抑制潜力和机理。酶动力学的结果表明4-己基间苯二酚以非竞争性方式可逆地抑制α-葡萄糖苷酶活性。然后，荧光猝灭表明它通过形成α-葡萄糖苷酶-己基间苯二酚复合物，增加了α-葡萄糖苷酶的疏水性并改变了酶的构象。热力学分析和分子对接进一步证明4-己基间苯二酚对α-葡萄糖苷酶的抑制作用主要取决于氢键和疏水相互作用。而且，4-己基间苯二酚适度抑制果糖胺的形成，并强烈抑制α-二羰基化合物和高级糖基化终产物（AGEs）的生成。4-己基间苯二酚和牛血清白蛋白之间的相互作用主要是由疏水相互作用驱动的。这项研究显示了一种新型的α-葡萄糖苷酶抑制剂以及非酶糖基化作用，并为预防和治疗2型糖尿病提供了候选药物。