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基于双香豆素骨架的高效α-葡萄糖苷酶抑制剂的合成与分子对接研究

Synthesis and molecular docking studies of potent α-glucosidase inhibitors based on biscoumarin skeleton.

作者信息

Khan Khalid Mohammed, Rahim Fazal, Wadood Abdul, Kosar Naveen, Taha Muhammad, Lalani Salima, Khan Aisha, Fakhri Muhammad Imran, Junaid Muhammad, Rehman Wajid, Khan Momin, Perveen Shahnaz, Sajid Muhammad, Choudhary M Iqbal

机构信息

H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.

Department of Chemistry, Hazara University, Mansehra, Pakistan.

出版信息

Eur J Med Chem. 2014 Jun 23;81:245-52. doi: 10.1016/j.ejmech.2014.05.010. Epub 2014 May 4.

Abstract

In our effort directed toward the discovery of new anti-diabetic agent for the treatment of diabetes, a library of biscoumarin derivative 1-18 was synthesized and evaluated for α-glucosidase inhibitory potential. All eighteen (18) compounds displayed assorted α-glucosidase activity with IC50 values 16.5-385.9 μM, if compared with the standard acarbose (IC50 = 906 ± 6.387 μM). In addition, molecular docking studies were carried out to explore the binding interactions of biscoumarin derivatives with the enzyme. This study has identified a new class of potent α-glucosidase inhibitors.

摘要

在我们致力于发现用于治疗糖尿病的新型抗糖尿病药物的过程中,合成了双香豆素衍生物1 - 18库,并对其α - 葡萄糖苷酶抑制潜力进行了评估。与标准阿卡波糖(IC50 = 906 ± 6.387 μM)相比,所有十八种(18)化合物均表现出不同的α - 葡萄糖苷酶活性,IC50值为16.5 - 385.9 μM。此外,还进行了分子对接研究,以探索双香豆素衍生物与该酶的结合相互作用。这项研究确定了一类新的强效α - 葡萄糖苷酶抑制剂。

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