Synthesis 4-[2-(2-mercapto-4-oxo-4H-quinazolin-3-yl)-ethyl]-benzenesulfonamides with subnanomolar carbonic anhydrase II and XII inhibitory properties

Bozdag, Murat and Alafeefy, Ahmed Mahmoud and Carta, Fabrizio and Ceruso, Mariangela and Al-Tamimi, Abdul-Malek S. and Al-Kahtani, Abdulla A. and Alasmary, Fatmah A.S. and Supuran, Claudiu T. (2016) Synthesis 4-[2-(2-mercapto-4-oxo-4H-quinazolin-3-yl)-ethyl]-benzenesulfonamides with subnanomolar carbonic anhydrase II and XII inhibitory properties. Bioorganic & Medicinal Chemistry, 24 (18). pp. 4100-4107. ISSN 0968-0896

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Abstract

Condensation of substituted anthranilic acids with 4-isothiocyanatoethyl-benzenesulfonamide led to series of heterocyclic benzenesulfonamides incorporating 2-mercapto-quinazolin-4-one tails. 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 XII (a transmembrane, tumor-associated enzyme also involved in glaucoma-genesis). The new sulfonamides acted as medium potency inhibitors of hCA I (KIs of 28.5– 2954 nM), being highly effective as hCA II (KIs in the range of 0.62–12.4 nM) and XII (KIs of 0.54– 7.11 nM) inhibitors. All substitution patterns present in these compounds (e.g., halogens, methyl and methoxy moieties, in positions 6, 7 and/or 8 of the 2-mercapto-quinazolin-4-one ring) led to highly effective hCA II/XII 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 isoforms CA II and XII is dysregulated.

Item Type:	Article (Journal)
Additional Information:	7668/51705
Uncontrolled Keywords:	Carbonic anhydrase; Sulfonamide; Inhibitor; 2-Mercapto-quinazolin-4-one; Tail approach
Subjects:	R Medicine > R Medicine (General)
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Science > Department of Chemistry
Depositing User:	Dr Ahmed Alafeefy
Date Deposited:	19 Aug 2016 15:58
Last Modified:	12 Apr 2017 10:03
URI:	http://irep.iium.edu.my/id/eprint/51705

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