Produção Nacional
Revisado por pares
Antiplatelet properties of novel N-substituted-phenyl-1,2,3-triazole-4-acylhydrazone derivatives
2003; Elsevier BV; Volume: 11; Issue: 9 Linguagem: Inglês
10.1016/s0968-0896(03)00055-5
ISSN1464-3391
AutoresAnna C. Cunha, Juliana M. Figueiredo, Jorge L. M. Tributino, Ana Luísa P. Miranda, Helena Carla Castro, Russolina B. Zingali, Carlos Alberto Manssour Fraga, Maria Cecília B. V. de Souza, Vı́tor F. Ferreira, Eliezer J. Barreiro,
Tópico(s)Synthesis and Reactions of Organic Compounds
ResumoThis paper describes the design, synthesis and pharmacological evaluation of new N-acylhydrazone (NAH) compounds, belonging to the N-substituted-phenyl-1,2,3-triazole-4-acylhydrazone class (2a–p). Classical heteroaromatic ring bioisosterism strategies were applied to the previously reported N-phenylpyrazolyl-4-acylhydrazone derivative 1, elected as lead-compound due to its important anti-aggregating profile on arachidonic acid induced platelet aggregation (IC50=24±0.5 μM), from which emerge this new series 2. These new compounds 2a–p were readily synthesized, characterized and tested on platelet aggregation assays induced by collagen (5 μg/mL), ADP (5 μM) and arachidonic acid (100 μM) in rabbit citrated platelet-rich plasma. Compounds 2b, 2d, and 2h were found to be the most potent, exhibiting a significant antiplatelet activity on arachidonic acid- and collagen-induced platelet aggregation. In addition, these new antiplatelet agents are free of gastric ulcerogenic effect and presented discrete anti-inflammatory and analgesic properties. The N-para-chlorophenyltriazolyl-4-acylhydrazone compound 2h produced the highest inhibitory effect on collagen (IC50=21.6±0.4 μM) and arachidonic acid-induced platelet aggregation (IC50=2.2±0.06 μM), suggesting that the nature of the substituent on the phenyl ring of the N-heteroaromatic system of NAH moiety may be an important structural requirement for the improvement of antiplatelet activity, in comparison with lead-series 1.
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