title: Synthesis and carbonic anhydrase inhibitory properties of novel uracil derivatives.
abstract: Carbonic anhydrase (CA) inhibitors are valuable molecules based on several therapeutic applications, including antiglaucoma activity. In the present study, inhibition of two human cytosolic carbonic anhydrase isozymes I and II with some uracil derivatives (3-9) were investigated. Compounds 3-9 showed KI values in the range of 10.83-464 μM for hCA I and of 28.88-778.5 μM against hCA II, respectively. Kinetic investigations showed that similarly to classical CA inhibitors, all investigated natural compounds act as competitive inhibitors with 4-NPA as substrate. Uracil derivatives investigated here are promising agents which may be used as lead molecules in order to derivative novel carbonic anhydrase inhibitors that might be useful in medical applications.
authors.affiliation: Ağrı İbrahim Çeçen University, Department of Chemistry, 04100 Ağrı, Turkey. Electronic address: mguney@agri.edu.tr.
authors.forename: Murat
authors.initials: M
authors.lastname: Güney
authors.affiliation: Dumlupinar University, Education Faculty, 43100 Kutahya, Turkey.
authors.forename: Hüseyin
authors.initials: H
authors.lastname: Çavdar
authors.affiliation: Ağrı İbrahim Çeçen University, Department of Chemistry, 04100 Ağrı, Turkey. Electronic address: msenturk@agri.edu.tr.
authors.forename: Murat
authors.initials: M
authors.lastname: Şentürk
authors.affiliation: Ondokuz Mayıs University, Department of Agricultural Biotechnology, 55139 Samsun, Turkey.
authors.forename: Deniz
authors.initials: D
authors.lastname: Ekinci
mesh_terms: D001667:Binding, Competitive; D024401:Carbonic Anhydrase I / Q000037:antagonists & inhibitors; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007700:Kinetics; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D014498:Uracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D014498:Uracil; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II
keywords: Carbonic anhydrase; Enzyme inhibitor; Hydroxyl; Uracil