1, 2, 3-Benzoxathiazine-2, 2-dioxides – effective inhibitors of human carbonic anhydrases. (1st January 2023)

• Record Type: Journal Article
• Authors: Ivanova, Jekaterina; Abdoli, Morteza; Nocentini, Alessio; Žalubovskis, Raivis; Supuran, Claudiu T.
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 38:Number 1(2023)
• Page Start: 225
• Page End: 238
• Publication Date: 2023-01-01
• Subjects: Carbonic anhydrase -- 123-benzoxathiazine 22-dioxide -- inhibitors; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2022.2142787
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: A series of 1, 2, 3-benzoxathiazine-2, 2-dioxides possessing various substituents in the 5, 7, or 8 position was obtained from corresponding 2-hydroxybenzaldehydes in their reaction with sulfamoyl chloride. 5-, 7-, and 8-aryl substituted 1, 2, 3-benzoxathiazine-2, 2-dioxides were prepared from aryl substituted 2-hydroxybenzaldehydes obtained from 3-, 4-, or 6-bromo-2-hydroxybenzaldehydes via two-step protocol. 1, 2, 3-Benzoxathiazine-2, 2-dioxides were investigated for the inhibition of four human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, cytosolic hCA I and II and tumour-associated transmembrane hCA IX and XII. Twenty four derivatives of 1, 2, 3-benzoxathiazine 2, 2-dioxide were obtained. Most of them act as nanomolar inhibitors of hCA IX and XII. Almost all compounds except 2d and 5a-e also express nanomolar inhibitory activity for hCA II. hCA I is poorly inhibited or not inhibited by 1, 2, 3-benzoxathiazine 2, 2-dioxides. Some of the new derivatives exhibit promising selectivity towards CA IX/XII over hCA I, although none of the compounds are selective towards CA IX/XII over both hCA I and II.