Anti-inflammatory potential of thienopyridines as possible alternative to NSAIDs.
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.
Pharmacology Division, Indian Institute of Chemical Technology (IICT), Tarnaka, Hyderabad, Andhra Pradesh-500607, India. kuncha_m@yahoo.com
Kuncha
K
Madhusudana
Boyapati
B
Shireesha
Vegi Ganga Modi
VG
Naidu
Sistla
S
Ramakrishna
Banda
B
Narsaiah
Akkinepally Raghuram
AR
Rao
Prakash V
PV
Diwan
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D006099:Granuloma / Q000188:drug therapy; D007213:Indomethacin / Q000494:pharmacology / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced; D058924:Thienopyridines / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D058924:Thienopyridines; D007213:Indomethacin