Isomeric benzoylpyrroleacetic acids: some structural aspects for aldose reductase inhibitory and anti-inflammatory activities.
A number of isomeric benzoylpyrroleacetic acids (1-6) were prepared and tested in vitro for rat lenses aldose reductase activity. These pyrrole derivatives are structurally related to the acidic nonsteroidal anti-inflammatory drugs. Therefore, their anti-inflammatory properties were also evaluated in the carrageenan-induced rat paw edema model. Inhibition of the aldose reductase enzyme was found to depend on the presence of both the benzoyl and acetic acid functionalities. Better activity resulted when these moieties were introduced at positions 1 and 3 of the pyrrole ring. However, for anti-inflammatory activity, the acetic acid group was not necessary and, in some cases, its presence resulted in a loss of activity. 3-Benzoylpyrrole-1-acetic acid (6) exhibited an IC50 of 2.5 microM in the aldose reductase assay which is comparable to that of alrestatin (1.5 microM). Compound 6, however, showed no anti-inflammatory activity at doses up to a 100 mg/kg, ip, in the rat paw model.
Demopoulos
V J
VJ
Department of Pharmaceutical Chemistry, School of Pharmacy, University of Thessaloniki, Greece.
Rekka
E
E
D000085:Acetates / Q000138:chemical synthesis / Q000494:pharmacology*; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000494:pharmacology*; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005260:Female; D066298:In Vitro Techniques; D007536:Isomerism; D007908:Lens, Crystalline / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
D000085:Acetates; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002351:Carrageenan; D000449:Aldehyde Reductase