Evaluation of anti-inflammatory and analgesic activity of a new class of biphenyl analogs in animal models of inflammation.
A new class of 4'-methylbiphenyl-2-(substituted phenyl)carboxamide derivatives had been previously evaluated in vivo for their anti-inflammatory activities in animal models of inflammation. In the present study, the most active compound of that series, compound 4e (4'-methylbiphenyl-2-(4-carboxy phenyl)carboxamide), was investigated in detail for its anti-inflammatory, analgesic and ulcerogenic potential. Pretreatment of rats with 4e (100 mg/kg) reduced carrageenan induced rat paw edema at 3 h compared to control group. Dose dependent percent inhibition of granuloma formation, exudate volume, total leukocyte count was observed in 4e (25, 50 and 100 mg/kg) and celecoxib (CAS 169590-42-5; 5 mg/kg) treated groups in the cotton pellet granuloma and granuloma pouch technique, respectively, in rats. C-reactive proteins were absent in the 4e treated group. Compound 4e inhibited acetic acid induced writhing dose dependently (10, 20 and 30 mg/kg). Compound 4e was inactive in the hot plate test. Gastric toxicity screening experiments showed that compound 4e, both after single and repeated oral administration, is devoid of any gastric irritation in rats. The LD50 was found to be more than 2000 mg/kg.
Rathi
Badal S
BS
Department of Pharmacology and Pharmaceutical Chemistry, Bharati Vidyapeeth Deemed University, Poona College of Pharmacy, Erandwane, Pune, Maharashtra, India.
Wagh
Nilesh K
NK
Bodhankar
Subhash L
SL
Kulkarni
Vithal M
VM
D019342:Acetic Acid; D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D001713:Biphenyl Compounds / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D002097:C-Reactive Protein / Q000378:metabolism; D000068579:Celecoxib; D005260:Female; D005528:Foot / Q000473:pathology; D005753:Gastric Mucosa / Q000473:pathology; D006099:Granuloma / Q000139:chemically induced / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced; D013449:Sulfonamides / Q000494:pharmacology
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001713:Biphenyl Compounds; D011720:Pyrazoles; D013449:Sulfonamides; D002097:C-Reactive Protein; D000068579:Celecoxib; D019342:Acetic Acid