Development of 3-(4-aminosulphonyl)-phenyl-2-mercapto-3H-quinazolin-4-ones as inhibitors of carbonic anhydrase isoforms involved in tumorigenesis and glaucoma. Issue 6 (15th March 2016)

• Record Type: Journal Article
• Authors: Alafeefy, Ahmed M.; Carta, Fabrizio; Ceruso, Mariangela; Al-Tamimi, Abdul-Malek S.; Al-Kahtani, Abdulla A.; Supuran, Claudiu T.
• Is Part Of: Bioorganic & medicinal chemistry. Volume 24:Issue 6(2016)
• Page Start: 1402
• Page End: 1407
• Publication Date: 2016-03-15
• Subjects: Carbonic anhydrase -- Quinazoline -- Sulfonamides -- Mercaptan -- Tumor-associated isoforms; 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.2016.02.011
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: A series of heterocyclic benzenesulfonamides incorporating 2-mercapto-3 H -quinazolin-4-one tails were prepared by condensation of substituted anthranilic acids with 4-isothiocyanato-benzenesulfonamide. These sulfonamides were investigated as inhibitors of the human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms hCA I and II (cytosolic isozymes), as well as hCA IX and XII (trans-membrane, tumor-associated enzymes). They acted as medium potency inhibitors of hCA I ( K I s of 81.0–3084 nM), being highly effective as hCA II ( K I s in the range of 0.25–10.8 nM), IX ( K I s of 3.7–50.4 nM) and XII ( K I s of 0.60–52.9 nM) inhibitors. These compounds should thus be of interest as preclinical candidates in pathologies in which the activity of these enzymes should be inhibited, such as glaucoma (CA II and XII as targets) or some tumors in which the activity of three isoforms (CA II, IX and XII) is dysregulated.