Synthesis of new 3-(2-mercapto-4-oxo-4H-quinazolin-3-yl)-benzenesulfonamides with strong inhibition properties against the tumor associated carbonic anhydrases IX and XII

Bozdag, Murat and Alafeefy, Ahmed Mahmoud and Altamimi, Abdul Malik and Carta, Fabrizio and Supuran,, Claudiu T. and Vullo, Daniela (2017) Synthesis of new 3-(2-mercapto-4-oxo-4H-quinazolin-3-yl)-benzenesulfonamides with strong inhibition properties against the tumor associated carbonic anhydrases IX and XII. Bioorganic & Medicinal Chemistry, 25 (10). pp. 2782-2788. ISSN 0968-0896 E-ISSN 1464-3391

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Abstract

We report a series of novel metanilamide-based derivatives 3a–q bearing the 2-mercapto-4-oxo-4H-quinazolin-3-yl moiety as tail. All compounds were synthesized by means of straightforward condensation procedures and were investigated in vitro for their inhibition potency against the human (h) carbonic anhydrase (CA; EC 4.2.1.1.1) isoforms I, II, IX and XII. Among all compounds tested the 6-iodo 3g and the 7-fluoro 3i derivatives were the most potent inhibitors against the tumor associated CA IX and XII isoform (KIs 1.5 and 2.7 nM respectively for the hCA IX and KIs 0.57 and 1.9 nM respectively for the hCA XII). The kinetic data reported here strongly support compounds of this type for their future development as radiotracers in tumor pathologies which are strictly dependent on the enzymatic activity of the hCA IX and XII isoforms.

Item Type:	Article (Journal)
Additional Information:	7668/57250
Uncontrolled Keywords:	Carbonic anhydrase inhibitors (CAIs); Quinazolines; Tumors; Imaging
Subjects:	Q Science > QD Chemistry
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:	02 Jan 2018 08:59
Last Modified:	21 Jun 2018 08:37
URI:	http://irep.iium.edu.my/id/eprint/57250

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