Naslov
6-Imino-2-thioxo-pyrimidinones as a new class of dipeptidyl peptidase IV inhibitors

Autori
Jelić, Dubravko ; Nujić, Krunoslav ; Stepanić, Višnja ; Krunoslav, Kovačević ; Verbanac, Donatella

Izvornik
Medicinal chemistry research (1054-2523) 20 (2011), 3; 339-345

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
DPP IV inhibitor ; pyrimidinone ; enzyme kinetics ; molecular docking ; cytotoxicity

Sažetak
Dipeptidyl peptidase IV is a glycoprotein which removes N-terminal dipeptides from physiologically relevant polypeptides. An homologous series of 6-imino-2-thioxo-5-{; ; [3, 4, 5-tris(methyloxy)phenyl]methyl}; ; -2, 5-dihydro-4(3H)-pyrimidinones has been tested for inhibition of DPP IV activity. The inhibitory effects at 0.1 mM were observed. Enzyme kinetic studies revealed that compounds inhibit DPP IV activity competitively. According to the molecular docking analysis, the inhibitors are anchored into the DPP IV hydrolytic site by interactions of the pyrimidinone core with Glu206, Tyr662, and Tyr547, with the alkyl chain entering the S1 pocket. We conclude that pyrimidinone-like compounds are a promising new scaffold for reversible inhibition of DPP IV.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Temeljne medicinske znanosti, Farmacija

POVEZANOST RADA