Phosphonamidates are the first phosphorus-based zinc binding motif to show inhibition of β-class carbonic anhydrases from bacteria, fungi, and protozoa
A primary strategy to combat antimicrobial resistance is the identification of novel therapeutic targets and anti-infectives with alternative mechanisms of action. The inhibition of the metalloenzymes carbonic anhydrases (CAs, EC 4.2.1.1) from pathogens (bacteria, fungi, and protozoa) was shown to p...
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doaj-f628026ede3742598c43c7be18b0234e2021-07-15T13:10:31ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742020-01-01351596410.1080/14756366.2019.16819871681987Phosphonamidates are the first phosphorus-based zinc binding motif to show inhibition of β-class carbonic anhydrases from bacteria, fungi, and protozoaSiham A. Alissa0Hanan A. Alghulikah1Zeid A. Alothman2Sameh M. Osman3Sonia Del Prete4Clemente Capasso5Alessio Nocentini6Claudiu T. Supuran7Chemistry Department, College of Science, Princess Nourah bint Abdulrahman UniversityChemistry Department, College of Science, Princess Nourah bint Abdulrahman UniversityChemistry Department, College of Science, King Saud UniversityChemistry Department, College of Science, King Saud UniversityIstituto di Bioscienze e Biorisorse, CNRIstituto di Bioscienze e Biorisorse, CNRNEUROFARBA Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, Sezione di Scienze Farmaceutiche e Nutraceutiche, Università degli Studi di FirenzeNEUROFARBA Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, Sezione di Scienze Farmaceutiche e Nutraceutiche, Università degli Studi di FirenzeA primary strategy to combat antimicrobial resistance is the identification of novel therapeutic targets and anti-infectives with alternative mechanisms of action. The inhibition of the metalloenzymes carbonic anhydrases (CAs, EC 4.2.1.1) from pathogens (bacteria, fungi, and protozoa) was shown to produce an impairment of the microorganism growth and virulence. As phosphonamidates have been recently validated as human α-CA inhibitors (CAIs) and no phosphorus-based zinc-binding group have been assessed to date against β-class CAs, herein we report an inhibition study with this class of compounds against β-CAs from pathogenic bacteria, fungi, and protozoa. Our data suggest that phosphonamidates are among the CAIs with the best selectivity for β-class over human isozymes, making them interesting leads for the development of new anti-infectives.http://dx.doi.org/10.1080/14756366.2019.1681987virulenceresistancecarbonic anhydraseinhibitionphosphonamidateselectivity |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Siham A. Alissa Hanan A. Alghulikah Zeid A. Alothman Sameh M. Osman Sonia Del Prete Clemente Capasso Alessio Nocentini Claudiu T. Supuran |
spellingShingle |
Siham A. Alissa Hanan A. Alghulikah Zeid A. Alothman Sameh M. Osman Sonia Del Prete Clemente Capasso Alessio Nocentini Claudiu T. Supuran Phosphonamidates are the first phosphorus-based zinc binding motif to show inhibition of β-class carbonic anhydrases from bacteria, fungi, and protozoa Journal of Enzyme Inhibition and Medicinal Chemistry virulence resistance carbonic anhydrase inhibition phosphonamidate selectivity |
author_facet |
Siham A. Alissa Hanan A. Alghulikah Zeid A. Alothman Sameh M. Osman Sonia Del Prete Clemente Capasso Alessio Nocentini Claudiu T. Supuran |
author_sort |
Siham A. Alissa |
title |
Phosphonamidates are the first phosphorus-based zinc binding motif to show inhibition of β-class carbonic anhydrases from bacteria, fungi, and protozoa |
title_short |
Phosphonamidates are the first phosphorus-based zinc binding motif to show inhibition of β-class carbonic anhydrases from bacteria, fungi, and protozoa |
title_full |
Phosphonamidates are the first phosphorus-based zinc binding motif to show inhibition of β-class carbonic anhydrases from bacteria, fungi, and protozoa |
title_fullStr |
Phosphonamidates are the first phosphorus-based zinc binding motif to show inhibition of β-class carbonic anhydrases from bacteria, fungi, and protozoa |
title_full_unstemmed |
Phosphonamidates are the first phosphorus-based zinc binding motif to show inhibition of β-class carbonic anhydrases from bacteria, fungi, and protozoa |
title_sort |
phosphonamidates are the first phosphorus-based zinc binding motif to show inhibition of β-class carbonic anhydrases from bacteria, fungi, and protozoa |
publisher |
Taylor & Francis Group |
series |
Journal of Enzyme Inhibition and Medicinal Chemistry |
issn |
1475-6366 1475-6374 |
publishDate |
2020-01-01 |
description |
A primary strategy to combat antimicrobial resistance is the identification of novel therapeutic targets and anti-infectives with alternative mechanisms of action. The inhibition of the metalloenzymes carbonic anhydrases (CAs, EC 4.2.1.1) from pathogens (bacteria, fungi, and protozoa) was shown to produce an impairment of the microorganism growth and virulence. As phosphonamidates have been recently validated as human α-CA inhibitors (CAIs) and no phosphorus-based zinc-binding group have been assessed to date against β-class CAs, herein we report an inhibition study with this class of compounds against β-CAs from pathogenic bacteria, fungi, and protozoa. Our data suggest that phosphonamidates are among the CAIs with the best selectivity for β-class over human isozymes, making them interesting leads for the development of new anti-infectives. |
topic |
virulence resistance carbonic anhydrase inhibition phosphonamidate selectivity |
url |
http://dx.doi.org/10.1080/14756366.2019.1681987 |
work_keys_str_mv |
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1721300989047209984 |