Inhibition studies on a panel of human carbonic anhydrases with N1-substituted secondary sulfonamides incorporating thiazolinone or imidazolone-indole tails

Being the primary sulfonamide among the most efficient zinc binding group (ZBG) to design inhibitors for the metallo-enzymes carbonic anhydrases (CA, EC 4.2.1.1), herein, we propose an investigation on four physiologically important human (h) CAs (hCA I, II, IV, and IX) with N1-substituted secondary...

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Main Authors: Fadi M. Awadallah, Silvia Bua, Walaa R. Mahmoud, Hossam H. Nada, Alessio Nocentini, Claudiu T. Supuran
Format: Article
Language:English
Published: Taylor & Francis Group 2018-01-01
Series:Journal of Enzyme Inhibition and Medicinal Chemistry
Subjects:
Online Access:http://dx.doi.org/10.1080/14756366.2018.1446432
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author Fadi M. Awadallah
Silvia Bua
Walaa R. Mahmoud
Hossam H. Nada
Alessio Nocentini
Claudiu T. Supuran
author_facet Fadi M. Awadallah
Silvia Bua
Walaa R. Mahmoud
Hossam H. Nada
Alessio Nocentini
Claudiu T. Supuran
author_sort Fadi M. Awadallah
collection DOAJ
description Being the primary sulfonamide among the most efficient zinc binding group (ZBG) to design inhibitors for the metallo-enzymes carbonic anhydrases (CA, EC 4.2.1.1), herein, we propose an investigation on four physiologically important human (h) CAs (hCA I, II, IV, and IX) with N1-substituted secondary sulfonamides incorporating thiazolinone or imidazolone-indole tails. The effect of the functionalisation of the sulfonamide group with five different substitution patterns, namely acetyl, pyridine, thiazole, pyrimidine, and carbamimidoyl, was evaluated in relation to the inhibition profile of the corresponding primary sulfonamide analogues. With most of these latter being nanomolar inhibitors of all four considered isoforms, a totally counterproductive effect on the inhibition potency can be ascribed to N1-functionalisations of the ZBG primary sulfonamide structure with pyridine, thiazole, and pyrimidine moieties. On the other hand, incorporation of less hindered groups, such as sulfonylacetamides and sulfonylguanidines, maintained a certain degree of activity dependent on the tailing moiety, with KIs spanning in the low micromolar range.
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spelling doaj.art-e43bcc7d87924f28a5cfa47d06aa8cff2022-12-22T03:42:30ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742018-01-0133162963810.1080/14756366.2018.14464321446432Inhibition studies on a panel of human carbonic anhydrases with N1-substituted secondary sulfonamides incorporating thiazolinone or imidazolone-indole tailsFadi M. Awadallah0Silvia Bua1Walaa R. Mahmoud2Hossam H. Nada3Alessio Nocentini4Claudiu T. Supuran5Cairo UniversityUniversity of FirenzeCairo UniversityBadr UniversityUniversity of FirenzeUniversity of FirenzeBeing the primary sulfonamide among the most efficient zinc binding group (ZBG) to design inhibitors for the metallo-enzymes carbonic anhydrases (CA, EC 4.2.1.1), herein, we propose an investigation on four physiologically important human (h) CAs (hCA I, II, IV, and IX) with N1-substituted secondary sulfonamides incorporating thiazolinone or imidazolone-indole tails. The effect of the functionalisation of the sulfonamide group with five different substitution patterns, namely acetyl, pyridine, thiazole, pyrimidine, and carbamimidoyl, was evaluated in relation to the inhibition profile of the corresponding primary sulfonamide analogues. With most of these latter being nanomolar inhibitors of all four considered isoforms, a totally counterproductive effect on the inhibition potency can be ascribed to N1-functionalisations of the ZBG primary sulfonamide structure with pyridine, thiazole, and pyrimidine moieties. On the other hand, incorporation of less hindered groups, such as sulfonylacetamides and sulfonylguanidines, maintained a certain degree of activity dependent on the tailing moiety, with KIs spanning in the low micromolar range.http://dx.doi.org/10.1080/14756366.2018.1446432Carbonic anhydrasesulfonamidesinhibitorindolezinc binding-group
spellingShingle Fadi M. Awadallah
Silvia Bua
Walaa R. Mahmoud
Hossam H. Nada
Alessio Nocentini
Claudiu T. Supuran
Inhibition studies on a panel of human carbonic anhydrases with N1-substituted secondary sulfonamides incorporating thiazolinone or imidazolone-indole tails
Journal of Enzyme Inhibition and Medicinal Chemistry
Carbonic anhydrase
sulfonamides
inhibitor
indole
zinc binding-group
title Inhibition studies on a panel of human carbonic anhydrases with N1-substituted secondary sulfonamides incorporating thiazolinone or imidazolone-indole tails
title_full Inhibition studies on a panel of human carbonic anhydrases with N1-substituted secondary sulfonamides incorporating thiazolinone or imidazolone-indole tails
title_fullStr Inhibition studies on a panel of human carbonic anhydrases with N1-substituted secondary sulfonamides incorporating thiazolinone or imidazolone-indole tails
title_full_unstemmed Inhibition studies on a panel of human carbonic anhydrases with N1-substituted secondary sulfonamides incorporating thiazolinone or imidazolone-indole tails
title_short Inhibition studies on a panel of human carbonic anhydrases with N1-substituted secondary sulfonamides incorporating thiazolinone or imidazolone-indole tails
title_sort inhibition studies on a panel of human carbonic anhydrases with n1 substituted secondary sulfonamides incorporating thiazolinone or imidazolone indole tails
topic Carbonic anhydrase
sulfonamides
inhibitor
indole
zinc binding-group
url http://dx.doi.org/10.1080/14756366.2018.1446432
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