Design, synthesis, biological evaluation and molecular docking studies of dabigatran analogs as potential thrombin inhibitors

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• 作者：Hai-Feng Chen ; Ming-Hui Dong ; Yu-Jie Ren…
• 关键词：Dabigatran analogs ; Thrombin inhibition ; Molecular docking
• 刊名：Journal of the Iranian Chemical Society
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：13
• 期：2
• 页码：347-357
• 全文大小：1,031 KB
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• 作者单位：Hai-Feng Chen (1)
  Ming-Hui Dong (1)
  Yu-Jie Ren (1)
  Fei Wang (1)
  
  1. School of Chemical and Environmental Engineering, Shanghai Institute of Technology, No. 100, Haiquan Road, Fengxian District, Shanghai, 201400, China
  
• 刊物主题：Analytical Chemistry; Inorganic Chemistry; Physical Chemistry; Biochemistry, general; Organic Chemistry;
• 出版者：Springer Berlin Heidelberg
• ISSN：1735-2428

文摘

A series of fluorinated dabigatran analogs were designed and synthesized. All the target compounds were characterized by 1H NMR, 13C NMR, and FT-ICR-MS. The thrombin inhibitory activities of the new synthesized compounds were also evaluated in vitro. The results show that compound 12a has the highest IC₅₀ of thrombin inhibition (IC₅₀ = 5.41 nM). Moreover, molecular docking simulation was carried out to elucidate the conformations of the compounds and key amino acid residues at the active site of thrombin protein. The results show there is an appropriate relationship between IC₅₀ and the docking scores for compounds 12a–e. We suggest that the hydrogen bond interaction between Asp189, Gly219 of thrombin and the compounds appear to play major role in thrombin inhibition. Keywords Dabigatran analogs Thrombin inhibition Molecular docking