Anti-inflammatory potential of thienopyridines as possible alternative to NSAIDs
Anti-inflammatory potential of thienopyridines as possible alternative to NSAIDs
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DOI：
10.1016/j.ejphar.2011.12.019
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发表时间：
2012-03-05
影响因子：
5
通讯作者：
Diwan, Prakash V.
中科院分区：
文献类型：
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作者：
Madhusudana, Kuncha;Shireesha, Boyapati;Diwan, Prakash V.
本研究旨在评价新合成的硫代吡啶类似物的抗炎和抗关节炎活性。采用角叉菜胶、右旋糖苷和花生四烯酸诱导的大鼠足肿胀模型(急性模型)、棉球肉芽肿模型(亚急性模型)和弗氏完全佐剂性关节炎模型(慢性模型)测定了硫代吡啶类化合物的抗炎活性。化合物BN-4、BN-14和BN-16在100 mg/kg剂量下对角叉菜胶和花生四烯酸诱导的大鼠足肿胀模型有明显的抑制作用，对实验大鼠肉芽肿组织形成和弗氏完全佐剂诱导的关节炎也有明显的抑制作用。这些硫代吡啶类似物对脂多糖(LPS)刺激的小鼠巨噬细胞的促炎介质如肿瘤坏死因子(TNF)-α、白介素1-β(IL-1β)和一氧化氮(NO)也有抑制作用。溃疡形成研究结果表明，BN-4、BN-14和BN-16与非类固醇抗炎药(NSAID)吲哚美辛相比，在大鼠体内的溃疡形成潜力较小。综上所述，新的硫代吡啶类似物有望作为低毒的抗炎药应用于急、慢性炎症性疾病。(C)2011年，由爱思唯尔出版。
The present study was designed to evaluate the anti-inflammatory and antiarthritic activity of the new synthetic thienopyridine analogs. The anti-inflammatory activity of thienopyridines was assayed by using carrageenan; dextran and arachidonic acid induced paw edema models (acute), cotton pellet granuloma model (Sub acute) and Freund's complete adjuvant induced arthritis (chronic) in experimental rats. The compounds BN-4, BN-14 and BN-16 have shown significant inhibition of edema in carrageenan and arachidonic acid induced paw edema model at a dose of 100 mg/kg compared to the dextran induced paw edema model and also showed significant inhibition in granuloma tissue formation and Freund's complete adjuvant induced arthritis in experimental rats. These thienopyridine analogs also inhibited the proinflammatory mediators such as Tumor necrosis factor (TNF)-alpha, Interleukin (IL)-1 beta and Nitric Oxide (NO) in Lipopolysaccharide (LPS) challenged murine macrophages. Ulcerogenecity study results revealed less ulcerogenic potential of BN-4, BN-14 and BN-16 compared to nonsteroidal anti-inflammatory drug (NSAID) indomethacin in rats. In conclusion, the new thienopyridine analogs were promising for the potential use as anti-inflammatory agents for both acute and chronic inflammatory disorders with low toxic effects. (C) 2011 Published by Elsevier B.V.