Jiangxi Key Laboratory of Natural Products and Functional Foods, Jiangxi Agricultural University, Nanchang, China.
College of Science, Jiangxi Agricultural University, Nanchang, China.
J Enzyme Inhib Med Chem. 2020 Dec;35(1):1879-1890. doi: 10.1080/14756366.2020.1826941.
A series of novel -alkyl-1-deoxynojirimycin derivatives were synthesised and evaluated for their in vitro α-glucosidase inhibitory activity to develop α-glucosidase inhibitors with high activity. All twenty compounds exhibited α-glucosidase inhibitory activity with IC values ranging from 30.0 ± 0.6 µM to 2000 µM as compared to standard acarbose (IC = 822.0 ± 1.5 µM). The most active compound was ∼27-fold more active than acarbose. Kinetic study revealed that compounds , , and were all competitive inhibitors on α-glucosidase with of 10 µM, 52 µM, and 150 µM, respectively. Molecular docking demonstrated that the high active inhibitors interacted with α-glucosidase by four types of interactions, including hydrogen bonds, π-π stacking interactions, hydrophobic interactions, and electrostatic interaction. Among all the interactions, the π-π stacking interaction and hydrogen bond played a significant role in a various range of activities of the compounds.
一系列新型-烷-1-去氧野尻霉素衍生物被合成并评估其体外α-葡萄糖苷酶抑制活性，以开发具有高活性的α-葡萄糖苷酶抑制剂。与标准阿卡波糖（IC=822.0±1.5μM）相比，所有 20 种化合物均表现出α-葡萄糖苷酶抑制活性，IC 值范围为 30.0±0.6μM 至 2000μM。最活性化合物的活性比阿卡波糖高约 27 倍。动力学研究表明，化合物、和都是α-葡萄糖苷酶的竞争性抑制剂，Ki 值分别为 10μM、52μM 和 150μM。分子对接表明，高活性抑制剂通过氢键、π-π 堆积相互作用、疏水相互作用和静电相互作用四种相互作用与α-葡萄糖苷酶相互作用。在所有相互作用中，π-π 堆积相互作用和氢键在化合物的各种活性中起着重要作用。
