College of Life Science and Key Laboratory of Functional Small Organic Molecule, Ministry of Education, Jiangxi Normal University, Nanchang, Jiangxi 330022, People's Republic of China.
College of Life Science and Key Laboratory of Functional Small Organic Molecule, Ministry of Education, Jiangxi Normal University, Nanchang, Jiangxi 330022, People's Republic of China.
J Biosci Bioeng. 2021 Mar;131(3):241-249. doi: 10.1016/j.jbiosc.2020.10.011. Epub 2020 Nov 13.
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制。酶动力学结果表明，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。荧光猝灭进一步表明，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表明，4-己基间苯二酚对α-葡萄糖苷酶的抑制主要依赖于氢键和疏水相互作用。此外，4-己基间苯二酚适度抑制果糖胺的形成，强烈抑制α-二羰基化合物和晚期糖基化终产物（AGEs）的产生。4-己基间苯二酚与牛血清白蛋白的相互作用主要由疏水相互作用驱动。该研究发现了一种新型的α-葡萄糖苷酶和非酶糖基化抑制剂，为 2 型糖尿病的预防和治疗提供了一种药物候选物。
