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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Taylor & Francis Group
2018-01-01
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Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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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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issn | 1475-6366 1475-6374 |
language | English |
last_indexed | 2024-04-12T07:15:28Z |
publishDate | 2018-01-01 |
publisher | Taylor & Francis Group |
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series | Journal of Enzyme Inhibition and Medicinal Chemistry |
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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