Type 2 diabetes mellitus (T2DM) is an important metabolic disorder for which there is an urgent need for new antidiabetic drugs. α-Glucosidase inhibition is an established protocol for T2DM therapy. Because hyperglycemia causes oxidative tissue damage, the development of agents with both α-glucosidase inhibition and antioxidant activity from natural or natural-derived polyphenols such derivatives of rosmarinic acid (RA) represents an attractive therapeutic option. We report a study on amides 1-10 derived from RA and their evaluation for yeast α-glucosidase inhibition and antioxidant activity (DPPH and ORAC tests). All amides showed higher inhibitory activity than that of RA, were by far more potent than the antidiabetic drug acarbose, and proved to be effective antioxidants. A molecular docking study displayed significant binding interactions of RA amides with the active site of α-glucosidase. This in silico optimization study led to the design and synthesis of amides 9 (IC50 = 42.3 μM) and 10 (IC50 = 35.2 μM), showing the most potent α-glucosidase inhibition and good antioxidative properties. A kinetic study showed that 10 acts as a mixed type inhibitor.

中文翻译：

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作为抗氧化剂和降血糖剂的迷迭香酰胺的合成。


2型糖尿病（T2DM）是一种重要的代谢性疾病，迫切需要新的抗糖尿病药物。 α-葡萄糖苷酶抑制是 T2DM 治疗的既定方案。由于高血糖会导致氧化组织损伤，因此从天然或天然衍生的多酚（例如迷迭香酸（RA）衍生物）开发具有α-葡萄糖苷酶抑制和抗氧化活性的药物代表了一种有吸引力的治疗选择。我们报告了一项关于源自 RA 的酰胺 1-10 的研究及其对酵母 α-葡萄糖苷酶抑制和抗氧化活性的评估（DPPH 和 ORAC 测试）。所有酰胺都表现出比 RA 更高的抑制活性，比抗糖尿病药物阿卡波糖更有效，并被证明是有效的抗氧化剂。分子对接研究显示 RA 酰胺与 α-葡萄糖苷酶活性位点具有显着的结合相互作用。这项计算机优化研究导致了酰胺 9 (IC50 = 42.3 μM) 和 10 (IC50 = 35.2 μM) 的设计和合成，显示出最有效的 α-葡萄糖苷酶抑制作用和良好的抗氧化特性。动力学研究表明 10 作为混合型抑制剂。