Antiplatelet and Antithrombotic Activities of Non-Steroidal Anti-Inflammatory Drugs Containing an N-Acyl Hydrazone Subunit

Abstract

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.

Novel N‐Substituted ((1H‐indol‐3‐yl)methylene)benzohydrazides and ((1H‐indol‐3‐yl)methylene)‐2‐phenylhydrazines: Synthesis and Antiplatelet Aggregation Activity

“…could be one of the first studies suggesting small hydrazine molecules as potential antiplatelet agents . Later studies by other groups led to the development of more diverse sets of hydrazine compounds with antiplatelet activity, mostly against AA‐induced platelet aggregation . Inspired by the mentioned reports, we started a series of studies focused on small‐molecule hydrazones and screened them for antiplatelet activity.…”

“…have reported some arylsulfunate acylhydrazone derivatives with anitiplatelet activity by interfering in AA and thrombin pathways . The antiplatelet aryl(aroyl)hydrazones of aromatic aldehydes and methyl ketones, N ‐substituted‐phenyl‐1,2,3‐triazole‐4‐acylhydrazones, benzylidene 10 H ‐phenotiazin‐1‐carbohydrazide, and nonsteroidal anti‐inflammatory drugs (NSAIDs) containing N ‐acylhydrazone fragment are some other examples of hydrazone derivatives with antiplatelet aggregation activities.…”

Leishmanicidal Activities of Novel Synthetic Furoxan and Benzofuroxan Derivatives

“…It has been described that the N-acyl hydrazone subunit could be unstable in acid media (58,59). So, in order to characterize the chemical stability of the most active compounds, 8a and 14a, we have performed chemical hydrolysis in vitro.…”

New approaches in tail‐bleeding assay in mice: improving an important method for designing new anti‐thrombotic agents

“…; Chelucci et al . ). As a result, bleeding time assays vary considerably between laboratories, which hinders fair comparison of new drug prototypes and may eventually cause the loss of potential drugs (Greene et al .…”

“…; Chelucci et al . ) or (ii) total amputation of the tip of the tail (transection model) (Dejana et al . ; Herbert & Bernat ; Tanaka et al .…”