Type 2 diabetes mellitus is a metabolic dreadful disease caused by an uncontrolled glucose level in the bloodstream, particularly high after a meal. Inhibitors of glucosidases, involved in the digestion of carbohydrates, can regulate this post-prandial increase in glucose concentration. The traditional drugs act as competitive inhibitors of both pancreatic α-amylase and α-glucosidases and this unselective inhibition is behind severe gastrointestinal side effects related to the concomitant inhibition of α-amylase. We described herein some perglycosylated cyclodextrins as efficient and selective inhibitors of α-glucosidase with low micromolar IC₅₀ (3.64-7.98 μM) compared to the acarbose (IC₅₀ 212 μM), clinically used for patients suffering from type 2 diabetes. On the other hand, they do not inhibit α-amylase (IC₅₀>500 μM). Structure/activity relationship rationalization suggests multiple interactions between the described inhibitors and α-glucosidase, which support the existence of both active site and allosteric interactions.

中文翻译：

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用于治疗 2 型糖尿病的新型选择性 α-葡萄糖苷酶抑制剂

2 型糖尿病是一种可怕的代谢疾病，由血液中血糖水平不受控制（尤其是餐后血糖水平升高）引起。参与碳水化合物消化的葡萄糖苷酶抑制剂可以调节餐后葡萄糖浓度的增加。传统药物充当胰腺 α-淀粉酶和 α-葡萄糖苷酶的竞争性抑制剂，这种非选择性抑制是与 α-淀粉酶同时抑制相关的严重胃肠道副作用的原因。我们在此描述了一些高糖基化环糊精作为有效且选择性的α-葡萄糖苷酶抑制剂，与阿卡波糖（IC ₅₀ 212 μM）相比，具有低微摩尔IC ₅₀ (3.64-7.98 μM) ，临床上用于患有2型糖尿病的患者。另一方面，它们不抑制 α-淀粉酶 (IC ₅₀ >500 μM)。结构/活性关系合理化表明所描述的抑制剂和α-葡萄糖苷酶之间存在多种相互作用，这支持活性位点和变构相互作用的存在。