In vitro evaluation of 5-arylidene-2-thioxo-4-thiazolidinones active as aldose reductase inhibitors.
2-Thioxo-4-thiazolidinone derivatives were evaluated as aldose reductase inhibitors (ARIs) and most of them exhibited good or excellent in vitro efficacy. Out of the tested compounds, most N-unsubstituted analogues were found to possess inhibitory effects at low micromolar doses and two of them exhibited higher potency than sorbinil, used as a reference drug. The insertion of an acetic chain on N-3 of the thiazolidinone scaffold led to analogues with submicromolar affinity for ALR2 and IC(50) values very similar to that of epalrestat, the only ARI currently used in therapy.
Dipartimento Farmaco-chimico, Faculty of Pharmacy, University of Messina, Polo Universitario Annunziata, 98168 Messina, Italy. rmaccari@pharma.unime.it
Rosanna
R
Maccari
Antonella
A
Del Corso
Marco
M
Giglio
Roberta
R
Moschini
Umberto
U
Mura
Rosaria
R
Ottanà
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D002417:Cattle; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D048289:Imidazolidines / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D045162:Thiazolidinediones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D004791:Enzyme Inhibitors; D048289:Imidazolidines; D045162:Thiazolidinediones; D000449:Aldehyde Reductase; C026411:sorbinil