Development of benzimidazole derivatives as novel anti-platelet drugs

Wei Cheng Yao, Lan Ting Yuan, Wen Bin Yang, Chih Hsuan Hsia, Li Ting Huang, Tzu Yin Lee, Joen Rong Sheu, Wan-Jung Lu, Thanasekaran Jayakumar, Ray Jade Chen

研究成果: 雜誌貢獻文章同行評審

2 引文 斯高帕斯(Scopus)


Background: Benzimidazoles are privileged biomolecules which form an integral part of vitamin B12 and have been attracting numerous researchers all over the world to assess their potential therapeutic significance. Objectives: The comparative in vitro antiplatelet activity of newly synthesized benzimidazole derivatives, M3BIM, C2BIM, and L2BIM in thrombin, adenosine diphosphate (ADP) and epinephrineinduced washed human platelets was investigated. Method: Reversed-phase silica gel column chromatography, Aggregometry, Flow cytometry and Immunoblotting were used in this study. Results: M3BIM exhibited a concentration (25-100 µM) dependent inhibitory effect on platelet aggregation induced by thrombin (0.01 U/mL) in washed human platelets and by epinephrine (10 µM) only at a maximum concentration of 500 µM in platelet-rich plasma (PRP); however, C2BIM and L2BIM had no response even at 500 µM against thrombin and 1mM against epinephrine-induced platelet aggregation. Moreover, all these three compounds were not inhibited platelet aggregation induced by ADP (20 µM). Additionally, these compounds showed no effects in thrombin-induced P-selectin expression and aIIbΒ3 activation, as evidenced by flow cytometry and clot reaction assays, respectively. Besides, M3BIM (100 µM) significantly abolished thrombin-induced Akt and mitogen-activated protein kinases (MAPKs) phosphorylation; whereas 200 µM C2BIM and L2BIM were not effective on these proteins. Conclusion: This study affords confirmation for the inhibitory effect of M3BIM in a low dose thrombin and epinephrine-induced platelet aggregation in vitro compared to other imidazole derivatives, C2BIM and L2BIM. These outcomes may recommend that M3BIM can be appraised as a prospective benzeimidazole compound for the treatment of thrombin -induced platelet defect and its related diseases.
頁(從 - 到)594-605
期刊Current Pharmaceutical Biotechnology
出版狀態已發佈 - 1月 1 2017

ASJC Scopus subject areas

  • 生物技術
  • 藥學科學


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