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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)594-605
Number of pages12
JournalCurrent Pharmaceutical Biotechnology
Volume18
Issue number7
DOIs
Publication statusPublished - Jan 1 2017

Fingerprint

Thrombin
Blood Platelets
Platelet Aggregation
Pharmaceutical Preparations
Epinephrine
Adenosine Diphosphate
Flow Cytometry
Benzimidazoles
Platelet-Rich Plasma
P-Selectin
Silica Gel
Vitamin B 12
benzimidazole
Mitogen-Activated Protein Kinases
Immunoblotting
Gel Chromatography
Phosphorylation
Research Personnel
Proteins

Keywords

  • ADP
  • Benzimidazole
  • Clot retraction
  • Epinephrine
  • MAPKs
  • P-selectin
  • Platelets
  • Thrombin

ASJC Scopus subject areas

  • Biotechnology
  • Pharmaceutical Science

Cite this

Development of benzimidazole derivatives as novel anti-platelet drugs. / Yao, Wei Cheng; Yuan, Lan Ting; Yang, Wen Bin; Hsia, Chih Hsuan; Huang, Li Ting; Lee, Tzu Yin; Sheu, Joen Rong; Lu, Wan-Jung; Jayakumar, Thanasekaran; Chen, Ray Jade.

In: Current Pharmaceutical Biotechnology, Vol. 18, No. 7, 01.01.2017, p. 594-605.

Research output: Contribution to journalArticle

Yao, Wei Cheng ; Yuan, Lan Ting ; Yang, Wen Bin ; Hsia, Chih Hsuan ; Huang, Li Ting ; Lee, Tzu Yin ; Sheu, Joen Rong ; Lu, Wan-Jung ; Jayakumar, Thanasekaran ; Chen, Ray Jade. / Development of benzimidazole derivatives as novel anti-platelet drugs. In: Current Pharmaceutical Biotechnology. 2017 ; Vol. 18, No. 7. pp. 594-605.
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AU - Huang, Li Ting

AU - Lee, Tzu Yin

AU - Sheu, Joen Rong

AU - Lu, Wan-Jung

AU - Jayakumar, Thanasekaran

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