Abstract | AIM: In the search for new antithrombotic drug candidates, the synthesis and anti-platelet activity of a new series of N-acylhydrazones that were designed as thrombin inhibitors has been previously described. The aim of this work was to further characterize the effects of these compounds on thrombin-induced platelet aggregation and induced thrombosis in vivo. METHODS: RESULTS: At 200 µM, the compounds showed between 36% and 82% inhibition (for L-743 and L-752, respectively) of thrombin-induced platelet aggregation. The receptor agonist of PAR-4, TRAP-4A (250 µM), was used and inhibition between 43% and 77% was observed for each compound (200 µM).Compounds LASSBio-752 and 743 were the most effective in the venous thrombosis model, increasing the survival of the treated animals to 63% and 46%, respectively, in the model of collagen-induced thromboembolism and increasing to 80% (both) in the thrombin-induced model. LASSBio 743 was more effective for deep vein thrombosis, reducing the weight of the thrombus by approximately 70%. CONCLUSION: All compounds were administered orally and have shown effective antithrombotic action independently of the thrombotic stimulus. These results indicate that compounds LASSBio-743 and 752 are potential candidates for the treatment of cardiovascular diseases.
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Authors | Flávia Serra Frattani, Eduardo Oliveira Coriolano, Lidia Moreira Lima, Eliezer Jesus Barreiro, Russolina Benedeta Zingali |
Journal | Journal of atherosclerosis and thrombosis
(J Atheroscler Thromb)
Vol. 20
Issue 3
Pg. 287-95
( 2013)
ISSN: 1880-3873 [Electronic] Japan |
PMID | 23182978
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antithrombins
- Hydrazones
- Platelet Aggregation Inhibitors
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Topics |
- Administration, Oral
- Animals
- Antithrombins
(administration & dosage, pharmacology, therapeutic use)
- Disease Models, Animal
- Hydrazones
(administration & dosage, chemistry, pharmacology, therapeutic use)
- Mice
- Platelet Aggregation Inhibitors
(administration & dosage, pharmacology, therapeutic use)
- Pulmonary Embolism
(drug therapy)
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