二苯并氮杂䓬类非糖基三唑的体外α-葡萄糖苷酶抑制作用、构效关系及分子对接
In vitro α-Glucosidase Inhibition by Non-sugar based Triazoles of Dibenzoazepine, their Structure-Activity Relationship, and Molecular Docking.
作者信息
Khan Maria A, Javaid Kulsoom, Wadood Abdul, Jamal Alam, Batool Farhana, Fazal-Ur-Rehman Saba, Basha Fatima Z, Choudhary Muhammad I
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 Biochemistry, Computational Medicinal Chemistry Laboratory, UCSS, Abdul Wali Khan University Mardan. Pakistan.
出版信息
Med Chem. 2017;13(7):698-704. doi: 10.2174/1573406413666170726142949.
BACKGROUND
α-Glucosidase inhibitors (AGIs) have been reported for their clinical potential against postprandial hyperglycemia, which is responsible for the risks associated with diabetes mellitus 2 and cardiovascular diseases (CVDs). Besides, a number of compounds have been reported as potent AGIs, several side effects are associated with them.
METHODS
The aim of present work is to explore new and potent molecules as AGIs. Therefore, a library of dibenzoazepine linked triazoles (1-15) was studied for their in vitro α-glucosidase inhibitory activity. The binding modes of potent compounds in the active site of α-glucosidase enzyme were also explored through molecular docking studies.
RESULTS AND CONCLUSION
Among the reported triazoles, compounds 3-9, 11, and 13 (IC50 = 6.0 ± 0.03 to 19.8 ± 0.28 µM) were found to be several fold more active than the standard drug acarbose (IC50 = 840 ± 1.73 µM). Compound 5 (IC50 = 6.0 ± 0.03 µM) was the most potent AGIs in the series, about 77- fold more active than acarbose. Therefore, dibenzoazepine linked-triazoles described here can serve as leads for further studies as new non-sugar AGIs.
背景
据报道，α-葡萄糖苷酶抑制剂（AGIs）具有对抗餐后高血糖的临床潜力，餐后高血糖是2型糖尿病和心血管疾病（CVDs）相关风险的原因。此外，已有多种化合物被报道为强效AGIs，但它们存在一些副作用。
方法
本研究的目的是探索新型强效的AGIs分子。因此，研究了二苯并氮杂䓬连接的三唑类化合物库（1-15）的体外α-葡萄糖苷酶抑制活性。还通过分子对接研究探索了强效化合物在α-葡萄糖苷酶活性位点的结合模式。
结果与结论
在所报道的三唑类化合物中，化合物3-9、11和13（IC50 = 6.0 ± 0.03至19.8 ± 0.28 μM）的活性比标准药物阿卡波糖（IC50 = 840 ± 1.73 μM）高几倍。化合物5（IC50 = 6.0 ± 0.03 μM）是该系列中最有效的AGIs，其活性比阿卡波糖高约77倍。因此，本文所述的二苯并氮杂䓬连接的三唑类化合物可作为新型非糖类AGIs进一步研究的先导化合物。
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