新型四环氧化吲哚衍生物作为α-葡萄糖苷酶抑制剂的设计、合成及对接研究
Design, synthesis and docking study of novel tetracyclic oxindole derivatives as α-glucosidase inhibitors.
作者信息
Han Kailin, Li Yashan, Zhang Yazhou, Teng Yuou, Ma Ying, Wang Meiyan, Wang Runling, Xu Weiren, Yao Qingwei, Zhang Yongmin, Qin Haijuan, Sun Hua, Yu Peng
机构信息
Key Laboratory of Industrial Fermentation Microbiology (Tianjin University of Science and Technology), Ministry of Education, Tianjin 300457, China; Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China; Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, Tianjin University of Science and Technology, Tianjin 300457, China.
Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.
出版信息
Bioorg Med Chem Lett. 2015 Apr 1;25(7):1471-5. doi: 10.1016/j.bmcl.2015.02.031. Epub 2015 Feb 21.
A series of novel tetracyclic oxindole derivatives were synthesized via tandem Suzuki coupling-Michael addition reaction catalyzed by palladium. Twenty derivatives were designed and synthesized in 6-8 steps in 8-20% overall yields. Their structures were confirmed by (1)H, (13)C NMR and LC/MS. These compounds were evaluated for α-glucosidase inhibitory activity in vitro. Compounds 7c, 7d, 7e, 7g, 7h, and 7i exhibited IC50 values of 32.3, 12.1, 15.7, 29.0, 16.0, and 4.8 μM, respectively, with potency all higher than that of the control standard acarbose (IC50=115.8 μM). Molecular docking studies revealed the existence of potential hydrogen bonding and hydrophobic interaction between the enzyme and the active compound 7i.
通过钯催化的串联铃木偶联-迈克尔加成反应合成了一系列新型四环氧化吲哚衍生物。设计并合成了20种衍生物，以8-20%的总收率经6-8步反应得到。通过(1)H、(13)C NMR和LC/MS确认了它们的结构。对这些化合物进行了体外α-葡萄糖苷酶抑制活性评估。化合物7c、7d、7e、7g、7h和7i的IC50值分别为32.3、12.1、15.7、29.0、16.0和4.8 μM，活性均高于对照标准阿卡波糖(IC50=115.8 μM)。分子对接研究表明，酶与活性化合物7i之间存在潜在的氢键和疏水相互作用。
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