Abstract

A series of novel N-alkyl-1-deoxynojirimycin derivatives 25 ∼ 44 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 IC₅₀ values ranging from 30.0 ± 0.6 µM to 2000 µM as compared to standard acarbose (IC₅₀ = 822.0 ± 1.5 µM). The most active compound 43 was ∼27-fold more active than acarbose. Kinetic study revealed that compounds 43, 40, and 34 were all competitive inhibitors on α-glucosidase with K_i 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.

摘要

一系列新颖的ñ -烷基-1-脱氧野尻霉素衍生物为25〜44，合成并评价了它们的体外α葡萄糖苷酶抑制活性，开发α葡萄糖苷酶具有高活性抑制剂。与标准阿卡波糖（IC ₅₀ = 822.0±1.5 µM）相比，所有二十种化合物均表现出α-葡萄糖苷酶抑制活性，IC ₅₀值为30.0±0.6 µM至2000 µM 。活性最高的化合物43比阿卡波糖高约27倍。动力学研究显示，化合物43，40，和34分别为在α葡糖苷所有竞争性抑制剂与ķ_我 分别为10 µM，52 µM和150 µM。分子对接表明，高活性抑制剂通过四种相互作用与α-葡萄糖苷酶相互作用，包括氢键，π-π堆积相互作用，疏水相互作用和静电相互作用。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重要作用。