白藜芦醇低聚物对人类唾液和胰腺α-淀粉酶的抑制作用

IF 6.8 1区医学 Q1 CHEMISTRY, MEDICINAL

Journal of Medicinal Chemistry Pub Date : 2024-11-05 DOI:10.1021/acs.jmedchem.4c0104210.1021/acs.jmedchem.4c01042

Rizliya Visvanathan, Dang Truong Le, Sushil Dhital, Topul Rali, Rohan A. Davis and Gary Williamson*,

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引用次数: 0

摘要

缓解餐后高血糖的一个关键策略是抑制α-淀粉酶，因为α-淀粉酶会启动肠道中的淀粉消化过程。本研究通过实验和分子对接研究，考察了白藜芦醇和类白藜芦醇四聚体、白藜芦醇 B、(-)-厚朴酚和白藜芦醇苷 A 对人类唾液和胰腺α-淀粉酶的抑制作用。Vaticanol B 的抑制作用最强，对唾液α-淀粉酶的 IC50 值为 5.3 ± 0.3 μM，对胰腺α-淀粉酶的 IC50 值为 6.1 ± 0.5 μM（相比之下，阿卡波糖的 IC50 值分别为 1.2 ± 0.1 μM 和 0.5 ± 0.0 μM）。动力学分析表明，白藜芦醇和白藜芦醇苷 A 对人类 α 淀粉酶的抑制作用较弱，而 (-)-hopeaphenol 则表现出中等程度的抑制作用。分子对接支持了抑制数据，结构构型的几个方面解释了龙脑香烷醇 B 产生更强抑制作用的原因。

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Inhibition of Human Salivary and Pancreatic α-Amylase by Resveratrol Oligomers

A key strategy to mitigate postprandial hyperglycemia involves inhibiting α-amylases, which commence the starch digestion process in the gut. This study examined the inhibitory effects of resveratrol and stilbenoid tetramers, vaticanol B, (−)-hopeaphenol, and vatalbinoside A on human salivary and pancreatic α-amylases experimentally and through molecular docking studies. Vaticanol B demonstrated the most potent inhibition with IC₅₀ values of 5.3 ± 0.3 μM for salivary and 6.1 ± 0.5 μM for pancreatic α-amylase (compared to acarbose with IC₅₀ values of 1.2 ± 0.1 μM and 0.5 ± 0.0 μM, respectively). Kinetic analysis suggested a competitive inhibition mode for vaticanol B. Resveratrol and vatalbinoside A were poor inhibitors of human α-amylases, while (−)-hopeaphenol exhibited moderate inhibition. Molecular docking supported the inhibition data, and several aspects of the structural configurations explained the stronger inhibition exerted by vaticanol B. Overall, vaticanol B shows promise as a natural alternative to acarbose for inhibiting α-amylase.

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来源期刊

Journal of Medicinal Chemistry 医学-医药化学

CiteScore

4.00

自引率

11.00%

发文量

804

审稿时长

1.9 months

期刊介绍： The Journal of Medicinal Chemistry is a prestigious biweekly peer-reviewed publication that focuses on the multifaceted field of medicinal chemistry. Since its inception in 1959 as the Journal of Medicinal and Pharmaceutical Chemistry, it has evolved to become a cornerstone in the dissemination of research findings related to the design, synthesis, and development of therapeutic agents. The Journal of Medicinal Chemistry is recognized for its significant impact in the scientific community, as evidenced by its 2022 impact factor of 7.3. This metric reflects the journal's influence and the importance of its content in shaping the future of drug discovery and development. The journal serves as a vital resource for chemists, pharmacologists, and other researchers interested in the molecular mechanisms of drug action and the optimization of therapeutic compounds.