Anti-inflammatory, antiproteolytic, and antihemolytic properties of pyrrole carboxylic acids.
Eight substituted pyrrole carboxylic acids were evaluated for their anti-inflammatory activity against carageenin-induced edema in rats. The protection afforded by seven of these compounds at a dose of 100 mg/kg i.p. ranged from 11 to 42%. Indomethacin (10 mg/kg i.p.), used as a reference drug, possessed 45% anti-inflammatory activity under similar experimental conditions. The ability of these compounds to exhibit in vitro antiproteolytic activity was reflected by their ability to inhibit trypsin-induced hydrolysis of bovine serum albumin. The inhibition of the activity of trypsin by these substituted pyrrole carboxylic acids (1 mM) ranged from 42 to 90% while such an inhibition with indomethacin (1 mM) was 95%. The in vitro membrane stabilizing property of these substituted pyrrole carboxylic acids was observed by their ability to provide protection against heat-induced dog erythrocyte hemolysis. The I50 value of these compounds, representing the concentration required to inhibit one-half of heat-induced erythrocyte hemolysis, ranged from 0.29 to 6.0 mM. Such an inhibition was concentration-dependent and biphasic in nature. The I50 value for indomethacin, showing greater antihemolytic activity was found to be 0.02 mM under similar experimental conditions. These results have provided some correlation of anti-inflammatory activity with antiproteolytic and membrane stabilizing properties for substituted pyrrole-3-carboxylic acids alone but not for pyrrole-2-carboxylic acids.
D000818:Animals; D000893:Anti-Inflammatory Agents; D002264:Carboxylic Acids / Q000494:pharmacology*; D006461:Hemolysis / Q000187:drug effects*; D008297:Male; D011480:Protease Inhibitors; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D000893:Anti-Inflammatory Agents; D002264:Carboxylic Acids; D011480:Protease Inhibitors; D011758:Pyrroles