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
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 αIIbβ3 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
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.