发现3,3-二（吲哚基）吲哚啉-2-酮作为α-葡萄糖苷酶抑制剂的新型骨架：计算机模拟研究和构效关系预测。
Discovery of 3,3-di(indolyl)indolin-2-one as a novel scaffold for α-glucosidase inhibitors: In silico studies and SAR predictions.
作者信息
Wang Guangcheng, Wang Jing, Xie Zhenzhen, Chen Ming, Li Luyao, Peng Yaping, Chen Shan, Li Wenbiao, Deng Bin
机构信息
College of Chemistry and Chemical Engineering, Hunan Engineering Laboratory for Analyse and Drugs Development of Ethnomedicine in Wuling Mountains, Jishou University, Jishou 416000, PR China.
College of Chemistry and Chemical Engineering, Hunan Engineering Laboratory for Analyse and Drugs Development of Ethnomedicine in Wuling Mountains, Jishou University, Jishou 416000, PR China.
出版信息
Bioorg Chem. 2017 Jun;72:228-233. doi: 10.1016/j.bioorg.2017.05.006. Epub 2017 May 3.
3,3-Di(indolyl)indolin-2-ones 4a-4n were synthesized and evaluated for their in vitro α-glucosidase inhibitory activity. These newly synthesized compounds showed moderate to potent α-glucosidase inhibitory activity with IC range from 5.98±0.11 to 145.95±0.46μM, when compared to the standard drug acarbose. Among this series of 3,3-di(indolyl)indolin-2-ones, compound 4j(5.98±0.11μM) having a 2-fluorobenzyl group on the indole ring was found to be the most active compound. Molecular docking studies showed that compound 4j have high binding affinities with the active site of α-glucosidase enzyme through hydrogen bonds, arene-cation, π-π stacking and hydrophobic interactions. This study showed these 3,3-di(indolyl)indolin-2-ones as a new class of α-glucosidase inhibitors.
合成了3,3-二（吲哚基）吲哚啉-2-酮4a - 4n，并对其体外α-葡萄糖苷酶抑制活性进行了评估。与标准药物阿卡波糖相比，这些新合成的化合物表现出中度至强效的α-葡萄糖苷酶抑制活性，IC范围为5.98±0.11至145.95±0.46μM。在这一系列3,3-二（吲哚基）吲哚啉-2-酮中，吲哚环上带有2-氟苄基的化合物4j（5.98±0.11μM）被发现是活性最高的化合物。分子对接研究表明，化合物4j通过氢键、芳基阳离子、π-π堆积和疏水相互作用与α-葡萄糖苷酶的活性位点具有高结合亲和力。这项研究表明这些3,3-二（吲哚基）吲哚啉-2-酮是一类新型的α-葡萄糖苷酶抑制剂。
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