Cardiovascular diseases, such as thrombosis and stroke,
represent the major cause of disability and death worldwide; and dysfunctions in
platelet aggregation and blood coagulation processes are involved. The regular antithrombotic
drugs have unsatisfactory results and may produce side effects.
Therefore, alternative therapies have been extensively investigated.
Objective: The anticoagulant and antiplatelet aggregation potential of a series of
six synthetic 1,2,3-triazole derivatives were investigated through in vitro models.
Methods: Coagulation tests included the prothrombin time (PT), activated partial
thromboplastin time (APTT) and thrombin time (TT) assays, and were performed
on a multichannel coagulometer, using human plasma. The platelet aggregation assays were carried
out using human platelet-rich-plasma (PRP). Aggregation was initiated by adding ADP or collagen
and monitored turbidimetrically on a Whole Blood Aggregometer. Toxicity of derivatives was
evaluated on platelets and red blood cells, by measuring the release of lactate dehydrogenase and
hemoglobin, respectively. Moreover, theoretical toxicity of derivatives was calculated using the
software Osiris® Property Explorer.
Results: All the six derivatives tested inhibited, but with different potencies, the plasma coagulation
assessed by the PT and TT assays, and also inhibited platelet aggregation of PRP induced by collagen
or ADP. The derivatives did not interfere in the aPTT assay and did not affect the viability of
platelets or red blood cells. Theoretical studies also revealed that all derivatives will likely to have
low toxicity, great pharmacological and oral bioavailability profiles, and a Druglikeness and Drug
score similar to some commercial anticoagulant and antiplatelet drugs.
Conclusion: 1,2,3-triazoles are potential candidates for molecular modeling of new antithrombotic