Substituted thiosemicarbazides and corresponding cyclized 1,3,4-oxadiazoles and their anti-inflammatory activity.
Several 1-(4-biphenoxyacetyl)-4-substituted arylthiosemicarbazides and their corresponding cyclized 2-(4-biphenoxymethyl)-5-arylamino-1,3,4- oxadiazoles were synthesized and characterized by elemental analyses and IR, mass, and nuclear magnetic resonance spectra. All compounds were evaluated for anti-inflammatory activity by determining their ability to provide protection against carrageenin-induced edema in rat paw. The anti-inflammatory activity possessed by substituted thiosemicarbazides [100 mg/kg, intraperitoneal(ip)] ranged from 22 to 68%, whereas substituted 1,3,4-oxadiazoles (100 mg/kg, ip) provided protection of 10-76%. Hydrocortisone (10 mg/kg, ip) and oxyphenbutazone (40 mg/kg, ip), used as standard reference drugs, decreased edema in rat paw by 44.6 and 52.9%, respectively. All compounds (1 mM) possessed antiproteolytic activity that was reflected by their ability to cause in vitro inhibition of trypsin-induced hydrolysis of bovine serum albumin. This inhibition ranged between 43 and 72% for substituted thiosemicarbazides and 30 and 83% for substituted 1,3,4-oxadiazoles.
Raman
K
K
Research Department, Alfred I. duPont Institute of the Nemours Foundation, Wilmington, DE 19899.
Singh
H K
HK
Salzman
S K
SK
Parmar
S S
SS
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology; D002351:Carrageenan; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005260:Female; D008297:Male; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013882:Thiosemicarbazones / Q000138:chemical synthesis* / Q000494:pharmacology; D014361:Trypsin Inhibitors / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010069:Oxadiazoles; D013882:Thiosemicarbazones; D014361:Trypsin Inhibitors; D012710:Serum Albumin, Bovine; D002351:Carrageenan