Antiplatelet and antithrombotic activities of non-steroidal anti-inflammatory drugs containing an N-acyl hydrazone subunit

Nonsteroidal anti-inflammatory drugs (NSAIDs) 1-5 containing an N-acyl hydrazone subunit were prepared and their antiplatelet and antithrombotic activities assessed in vitro and in vivo. Compounds 1-5 inhibited the platelet aggregation induced by adenosine diphosphate and/or arachidonic acid, with i...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2014-02, Vol.19 (2), p.2089-2099
Main Authors: Chelucci, Rafael Consolin, Dutra, Luiz Antônio, Lopes Pires, Maria Elisa, de Melo, Thais Regina Ferreira, Bosquesi, Priscila Longhin, Chung, Man Chin, Dos Santos, Jean Leandro
Format: Article
Language:English
Subjects:
Acids
Adenosine diphosphate
Analgesics
Animals
Anti-inflammatory agents
Anti-Inflammatory Agents, Non-Steroidal - administration & dosage
antiplatelet
antithrombotic
Arachidonic Acid - toxicity
Arthritis
Aspirin
bleeding time
Blood clots
Cardiovascular disease
Disease prevention
Drug dosages
Heart attacks
Hemorrhage - chemically induced
Hemorrhage - drug therapy
Hemorrhage - pathology
hydrazone
Hydrazones - administration & dosage
Inflammatory diseases
Mice
Nonsteroidal anti-inflammatory drugs
NSAIDs
Oral administration
Platelet Aggregation - drug effects
Platelet Aggregation Inhibitors - administration & dosage
Stroke
Thromboembolism
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Summary:Nonsteroidal anti-inflammatory drugs (NSAIDs) 1-5 containing an N-acyl hydrazone subunit were prepared and their antiplatelet and antithrombotic activities assessed in vitro and in vivo. Compounds 1-5 inhibited the platelet aggregation induced by adenosine diphosphate and/or arachidonic acid, with inhibition rates of 18.0%-61.1% and 65.9%-87.3%, respectively. Compounds 1 and 5 were the most active compounds, inhibiting adenosine-diphosphate-induced platelet aggregation by 57.2% and 61.1%, respectively. The inhibitory rates for arachidonic-acid-induced platelet aggregation were similar for compound 2 (80.8%) and acetylsalicylic acid (ASA, 80%). After their oral administration to mice, compounds 1, 3, and 5 showed shorter mean bleeding times than ASA. Compounds 1 and 5 also protected against thromboembolic events, with survival rates of 40% and 33%, respectively, compared with 30% for ASA. In conclusion, these results indicate that these novel NSAIDs containing an NAH subunit may offer better antiplatelet and antithrombotic activities than ASA.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules19022089