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

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) isofor...

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Main Authors:	Bozdag, Murat, Alafeefy, Ahmed Mahmoud, Carta, Fabrizio, Ceruso, Mariangela, Al-Tamimi, Abdul-Malek S., Al-Kahtani, Abdulla A., Alasmary, Fatmah A.S., Supuran, Claudiu T.
Format:	Article
Language:	English English English
Published:	Elsevier 2016
Subjects:	R Medicine (General)
Online Access:	http://irep.iium.edu.my/51705/ http://irep.iium.edu.my/51705/ http://irep.iium.edu.my/51705/ http://irep.iium.edu.my/51705/1/2016_4100-4107.pdf http://irep.iium.edu.my/51705/4/51705_benzenesulfonamides%20with%20subnanomolar%20carbonic_Scopus.pdf http://irep.iium.edu.my/51705/5/51705_benzenesulfonamides%20with%20subnanomolar%20carbonic_WoS.pdf

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spelling	iium-517052017-04-12T02:03:28Z http://irep.iium.edu.my/51705/ Synthesis 4-[2-(2-mercapto-4-oxo-4H-quinazolin-3-yl)-ethyl]-benzenesulfonamides with subnanomolar carbonic anhydrase II and XII inhibitory properties Bozdag, Murat Alafeefy, Ahmed Mahmoud Carta, Fabrizio Ceruso, Mariangela Al-Tamimi, Abdul-Malek S. Al-Kahtani, Abdulla A. Alasmary, Fatmah A.S. Supuran, Claudiu T. R Medicine (General) 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. Elsevier 2016-09-15 Article PeerReviewed application/pdf en http://irep.iium.edu.my/51705/1/2016_4100-4107.pdf application/pdf en http://irep.iium.edu.my/51705/4/51705_benzenesulfonamides%20with%20subnanomolar%20carbonic_Scopus.pdf application/pdf en http://irep.iium.edu.my/51705/5/51705_benzenesulfonamides%20with%20subnanomolar%20carbonic_WoS.pdf 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 http://www.sciencedirect.com/science/article/pii/S0968089616304758 10.1016/j.bmc.2016.06.052
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English English English
topic	R Medicine (General)
spellingShingle	R Medicine (General) Bozdag, Murat Alafeefy, Ahmed Mahmoud Carta, Fabrizio Ceruso, Mariangela Al-Tamimi, Abdul-Malek S. Al-Kahtani, Abdulla A. Alasmary, Fatmah A.S. Supuran, Claudiu T. Synthesis 4-[2-(2-mercapto-4-oxo-4H-quinazolin-3-yl)-ethyl]-benzenesulfonamides with subnanomolar carbonic anhydrase II and XII inhibitory properties
description	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.
format	Article
author	Bozdag, Murat Alafeefy, Ahmed Mahmoud Carta, Fabrizio Ceruso, Mariangela Al-Tamimi, Abdul-Malek S. Al-Kahtani, Abdulla A. Alasmary, Fatmah A.S. Supuran, Claudiu T.
author_facet	Bozdag, Murat Alafeefy, Ahmed Mahmoud Carta, Fabrizio Ceruso, Mariangela Al-Tamimi, Abdul-Malek S. Al-Kahtani, Abdulla A. Alasmary, Fatmah A.S. Supuran, Claudiu T.
author_sort	Bozdag, Murat
title	Synthesis 4-[2-(2-mercapto-4-oxo-4H-quinazolin-3-yl)-ethyl]-benzenesulfonamides with subnanomolar carbonic anhydrase II and XII inhibitory properties
title_short	Synthesis 4-[2-(2-mercapto-4-oxo-4H-quinazolin-3-yl)-ethyl]-benzenesulfonamides with subnanomolar carbonic anhydrase II and XII inhibitory properties
title_full	Synthesis 4-[2-(2-mercapto-4-oxo-4H-quinazolin-3-yl)-ethyl]-benzenesulfonamides with subnanomolar carbonic anhydrase II and XII inhibitory properties
title_fullStr	Synthesis 4-[2-(2-mercapto-4-oxo-4H-quinazolin-3-yl)-ethyl]-benzenesulfonamides with subnanomolar carbonic anhydrase II and XII inhibitory properties
title_full_unstemmed	Synthesis 4-[2-(2-mercapto-4-oxo-4H-quinazolin-3-yl)-ethyl]-benzenesulfonamides with subnanomolar carbonic anhydrase II and XII inhibitory properties
title_sort	synthesis 4-[2-(2-mercapto-4-oxo-4h-quinazolin-3-yl)-ethyl]-benzenesulfonamides with subnanomolar carbonic anhydrase ii and xii inhibitory properties
publisher	Elsevier
publishDate	2016
url	http://irep.iium.edu.my/51705/ http://irep.iium.edu.my/51705/ http://irep.iium.edu.my/51705/ http://irep.iium.edu.my/51705/1/2016_4100-4107.pdf http://irep.iium.edu.my/51705/4/51705_benzenesulfonamides%20with%20subnanomolar%20carbonic_Scopus.pdf http://irep.iium.edu.my/51705/5/51705_benzenesulfonamides%20with%20subnanomolar%20carbonic_WoS.pdf
first_indexed	2023-09-18T21:13:16Z
last_indexed	2023-09-18T21:13:16Z
_version_	1777411394193326080

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

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