Kinetic and X-ray crystallographic investigations of substituted 2-thio-6-oxo-1, 6-dihydropyrimidine–benzenesulfonamides acting as carbonic anhydrase inhibitors. Issue 16 (15th August 2016)

• Record Type: Journal Article
• Authors: Vullo, Daniela; Supuran, Claudiu T.; Scozzafava, Andrea; De Simone, Giuseppina; Monti, Simona Maria; Alterio, Vincenzo; Carta, Fabrizio
• Is Part Of: Bioorganic & medicinal chemistry. Volume 24:Issue 16(2016)
• Page Start: 3643
• Page End: 3648
• Publication Date: 2016-08-15
• Subjects: Carbonic anhydrase (CA) -- X-ray crystallography -- Sulfonamides -- 2-Thio-6-oxo-1, 6-dihydropyrimidines; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2016.06.005
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Herein we report an in vitro kinetic evaluation against the most relevant human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms (I, II, IX and XII) of a small series of lactate dehydrogenase (LDH, EC 1.1.1.27) inhibitors. All compounds contain a primary sulfonamide zinc-binding group (ZBG) substituted with the 2-thio-6-oxo-1, 6-dihydropyrimidine scaffold. By means of X-ray crystallographic experiments we explored the ligand–enzyme binding modes, thus highlighting the contribution of the 2-thio-6-oxo-1, 6-dihydropyrimidine moiety to the stabilization of the complex.