Antiinflammatory and antiproteolytic properties of naphthlthiosemicarbazides and cyclized oxadiazoles.
Eight 1-(naphth-1-ylacetyl)-4-substituted thiosemicarbazides and eight 2-(naphth-1-ylmethyl)-5-arylamino-1,3,4-oxadiazoles were synthesized and evaluated for antiinflammatory and antiproteolytic properties. All thiosemicarbazides (100 mg/kg) provided 14-43% protection against carrageenin-induced edema in rats. Cyclization of thiosemicarbazides to oxadiazoles resulted in significant reduction in the antiinflammatory activity. Some of these thiosemicarbazides also possessed low antiinflammatory activity against cotton-pellet-induced granuloma formation and formaldehyde-induced arthritis in rats. Hydrocortisone and oxyphenbutazone, used as reference drugs, exhibited greater antiinflammatory activity. All compounds possessed antiproteolytic activity. The in vitro protection of trypsin-induced hydrolysis of bovine serum albumin, unlike antiinflammatory activity, was greater with oxadiazoles (30-90%) than the precursor thiosemicarbazides (4-50%) at a final concentration of 1 mM.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000627:therapeutic use*; D001168:Arthritis / Q000188:drug therapy; D004487:Edema / Q000188:drug therapy; D006099:Granuloma / Q000188:drug therapy; D051379:Mice; D009281:Naphthalenes / Q000138:chemical synthesis / Q000627:therapeutic use; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000627:therapeutic use*; D051381:Rats; D012663:Semicarbazides / Q000138:chemical synthesis / Q000627:therapeutic use*; D014361:Trypsin Inhibitors / Q000138:chemical synthesis / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D009281:Naphthalenes; D010069:Oxadiazoles; D012663:Semicarbazides; D014361:Trypsin Inhibitors