Pharmacology Division, Indian Institute of Chemical Technology (IICT), Tarnaka, Hyderabad, Andhra Pradesh-500607, India.
Eur J Pharmacol. 2012 Mar 5;678(1-3):48-54. doi: 10.1016/j.ejphar.2011.12.019. Epub 2011 Dec 24.
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 100mg/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)-α, Interleukin (IL)-1β 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.
本研究旨在评估新型噻吩并吡啶类似物的抗炎和抗关节炎活性。噻吩并吡啶的抗炎活性通过角叉菜胶；葡聚糖和花生四烯酸诱导的爪肿胀模型（急性）、棉绒肉芽肿模型（亚急性）和完全弗氏佐剂诱导的关节炎（慢性）在实验大鼠中进行评估。化合物 BN-4、BN-14 和 BN-16 在 100mg/kg 剂量下对角叉菜胶和花生四烯酸诱导的爪肿胀模型显示出显著的抑制水肿作用，与葡聚糖诱导的爪肿胀模型相比，也显示出对肉芽肿组织形成和完全弗氏佐剂诱导的关节炎的显著抑制作用。这些噻吩并吡啶类似物还抑制了脂多糖（LPS）刺激的小鼠巨噬细胞中促炎介质如肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β和一氧化氮（NO）的产生。溃疡发生研究结果表明，与非甾体抗炎药（NSAID）吲哚美辛相比，BN-4、BN-14 和 BN-16 在大鼠中的致溃疡潜力较小。总之，新型噻吩并吡啶类似物具有作为急性和慢性炎症性疾病的抗炎药物的潜力，且毒性作用低。
