新型色酮-异吲哚酮衍生物的合成、体外α-葡萄糖苷酶抑制活性及对接研究
Synthesis, in vitro α-glucosidase inhibitory activity and docking studies of novel chromone-isatin derivatives.
作者信息
Wang Guangcheng, Chen Ming, Qiu Jie, Xie Zhenzhen, Cao Anbai
机构信息
Provincial Key Laboratory of Pharmaceutics in Guizhou Province, Guizhou Medical University, 4 Beijing Road, Guiyang 550004, China; School of Pharmacy, Guizhou Medical University, 4 Beijing Road, Guiyang 550004, China; National Engineering Research Center of Miao's Medicines, 4 Beijing Road, Guiyang 550004, China.
College of Chemistry and Chemical Engineering, Hunan Engineering Laboratory for Analyse and Drugs Development of Ethnomedicine in Wuling Mountains, Jishou University, Jishou 416000, China.
出版信息
Bioorg Med Chem Lett. 2018 Jan 15;28(2):113-116. doi: 10.1016/j.bmcl.2017.11.047. Epub 2017 Nov 28.
A novel series of chromone-isatin derivatives 6a-6p were designed, synthesized and characterized by H NMR, C NMR and HRMS. These novel synthetic compounds were evaluated for inhibitory activity against yeast α-glucosidase enzyme. The results of biological test have shown that all tested compounds exhibited excellent to potent inhibitory activity in the range of IC = 3.18 ± 0.12-16.59 ± 0.17 μM as compared to the standard drug acarbose (IC = 817.38 ± 6.27 μM). Compound 6j (IC = 3.18 ± 0.12 μM) with a hydroxyl group at the 7-position of chromone and a 4-bromobenzyl group at the N1-positions of isatin, was found to be the most active compound among the series. Furthermore, molecular docking study was performed to help understand binding interactions of the most active analogs with α-glucosidase enzyme. These results indicated that this class of compounds had potential for the development of anti-diabetic agents.
设计、合成了一系列新型色酮 - 异吲哚酮衍生物6a - 6p，并通过氢核磁共振（¹H NMR）、碳核磁共振（¹³C NMR）和高分辨质谱（HRMS）对其进行了表征。对这些新型合成化合物进行了抗酵母α - 葡萄糖苷酶活性的评估。生物测试结果表明，与标准药物阿卡波糖（IC₅₀ = 817.38 ± 6.27 μM）相比，所有测试化合物在IC₅₀ = 3.18 ± 0.12 - 16.59 ± 0.17 μM范围内均表现出优异至强效的抑制活性。在色酮的7位带有羟基且在异吲哚酮的N1位带有4 - 溴苄基的化合物6j（IC₅₀ = 3.18 ± 0.12 μM）被发现是该系列中活性最强的化合物。此外，进行了分子对接研究以帮助理解最具活性的类似物与α - 葡萄糖苷酶的结合相互作用。这些结果表明这类化合物具有开发抗糖尿病药物的潜力。
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