The Effect of Substituted Benzene-Sulfonamides and Clinically Licensed Drugs on the Catalytic Activity of CynT2, a Carbonic Anhydrase Crucial for <i>Escherichia coli </i>Life Cycle
Proteins are relevant antimicrobial drug targets, and among them, enzymes represent a significant group, since most of them catalyze reactions essential for supporting the central metabolism, or are necessary for the pathogen vitality. Genomic exploration of pathogenic and non-pathogenic microorgani...
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doaj-7cc58bffa90c4e38aa4abe99cdf96ffe2020-11-25T03:11:55ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-06-01214175417510.3390/ijms21114175The Effect of Substituted Benzene-Sulfonamides and Clinically Licensed Drugs on the Catalytic Activity of CynT2, a Carbonic Anhydrase Crucial for <i>Escherichia coli </i>Life CycleSonia Del Prete0Viviana De Luca1Silvia Bua2Alessio Nocentini3Vincenzo Carginale4Claudiu T. Supuran5Clemente Capasso6Institute of Biosciences and Bioresources, CNR, Via Pietro Castellino 111, 80131 Napoli, Italy, <email>sonia.delprete@ibbr.cnr.it</email> (S.D.P.)Institute of Biosciences and Bioresources, CNR, Via Pietro Castellino 111, 80131 Napoli, Italy, <email>sonia.delprete@ibbr.cnr.it</email> (S.D.P.)Section of Pharmaceutical and Nutraceutical Sciences, Department of Neurofarba, University of Florence, Via U. Schiff 6, Sesto Fiorentino, 50019 Florence, Italy, <email>silvia.bua@unifi.it</email> (S.B.)Section of Pharmaceutical and Nutraceutical Sciences, Department of Neurofarba, University of Florence, Via U. Schiff 6, Sesto Fiorentino, 50019 Florence, Italy, <email>silvia.bua@unifi.it</email> (S.B.)Institute of Biosciences and Bioresources, CNR, Via Pietro Castellino 111, 80131 Napoli, Italy, <email>sonia.delprete@ibbr.cnr.it</email> (S.D.P.)Section of Pharmaceutical and Nutraceutical Sciences, Department of Neurofarba, University of Florence, Via U. Schiff 6, Sesto Fiorentino, 50019 Florence, Italy, <email>silvia.bua@unifi.it</email> (S.B.)Institute of Biosciences and Bioresources, CNR, Via Pietro Castellino 111, 80131 Napoli, Italy, <email>sonia.delprete@ibbr.cnr.it</email> (S.D.P.)Proteins are relevant antimicrobial drug targets, and among them, enzymes represent a significant group, since most of them catalyze reactions essential for supporting the central metabolism, or are necessary for the pathogen vitality. Genomic exploration of pathogenic and non-pathogenic microorganisms has revealed genes encoding for a superfamily of metalloenzymes, known as carbonic anhydrases (CAs, EC 4.2.1.1). CAs catalyze the physiologically crucial reversible reaction of the carbon dioxide hydration to bicarbonate and protons. Herein, we investigated the sulfonamide inhibition profile of the recombinant ?-CA (CynT2) identified in the genome of the Gram-negative bacterium <i>Escherichia coli</i>. This biocatalyst is indispensable for the growth of the microbe at atmospheric pCO<sub>2</sub>. Surprisingly, this enzyme has not been investigated for its inhibition with any class of CA inhibitors. Here, we show that CynT2 was strongly inhibited by some substituted benzene-sulfonamides and the clinically used inhibitor sulpiride (K<sub>I</sub>s in the range of 82–97 nM). This study may be relevant for identifying novel CA inhibitors, as well as for another essential part of the drug discovery pipeline, such as the structure–activity relationship for this class of enzyme inhibitors.https://www.mdpi.com/1422-0067/21/11/4175carbonic anhydrasesulfonamidesinhibitorsantibacterials<i>Escherichia coli</i>stopped-flow assay |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sonia Del Prete Viviana De Luca Silvia Bua Alessio Nocentini Vincenzo Carginale Claudiu T. Supuran Clemente Capasso |
spellingShingle |
Sonia Del Prete Viviana De Luca Silvia Bua Alessio Nocentini Vincenzo Carginale Claudiu T. Supuran Clemente Capasso The Effect of Substituted Benzene-Sulfonamides and Clinically Licensed Drugs on the Catalytic Activity of CynT2, a Carbonic Anhydrase Crucial for <i>Escherichia coli </i>Life Cycle International Journal of Molecular Sciences carbonic anhydrase sulfonamides inhibitors antibacterials <i>Escherichia coli</i> stopped-flow assay |
author_facet |
Sonia Del Prete Viviana De Luca Silvia Bua Alessio Nocentini Vincenzo Carginale Claudiu T. Supuran Clemente Capasso |
author_sort |
Sonia Del Prete |
title |
The Effect of Substituted Benzene-Sulfonamides and Clinically Licensed Drugs on the Catalytic Activity of CynT2, a Carbonic Anhydrase Crucial for <i>Escherichia coli </i>Life Cycle |
title_short |
The Effect of Substituted Benzene-Sulfonamides and Clinically Licensed Drugs on the Catalytic Activity of CynT2, a Carbonic Anhydrase Crucial for <i>Escherichia coli </i>Life Cycle |
title_full |
The Effect of Substituted Benzene-Sulfonamides and Clinically Licensed Drugs on the Catalytic Activity of CynT2, a Carbonic Anhydrase Crucial for <i>Escherichia coli </i>Life Cycle |
title_fullStr |
The Effect of Substituted Benzene-Sulfonamides and Clinically Licensed Drugs on the Catalytic Activity of CynT2, a Carbonic Anhydrase Crucial for <i>Escherichia coli </i>Life Cycle |
title_full_unstemmed |
The Effect of Substituted Benzene-Sulfonamides and Clinically Licensed Drugs on the Catalytic Activity of CynT2, a Carbonic Anhydrase Crucial for <i>Escherichia coli </i>Life Cycle |
title_sort |
effect of substituted benzene-sulfonamides and clinically licensed drugs on the catalytic activity of cynt2, a carbonic anhydrase crucial for <i>escherichia coli </i>life cycle |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2020-06-01 |
description |
Proteins are relevant antimicrobial drug targets, and among them, enzymes represent a significant group, since most of them catalyze reactions essential for supporting the central metabolism, or are necessary for the pathogen vitality. Genomic exploration of pathogenic and non-pathogenic microorganisms has revealed genes encoding for a superfamily of metalloenzymes, known as carbonic anhydrases (CAs, EC 4.2.1.1). CAs catalyze the physiologically crucial reversible reaction of the carbon dioxide hydration to bicarbonate and protons. Herein, we investigated the sulfonamide inhibition profile of the recombinant ?-CA (CynT2) identified in the genome of the Gram-negative bacterium <i>Escherichia coli</i>. This biocatalyst is indispensable for the growth of the microbe at atmospheric pCO<sub>2</sub>. Surprisingly, this enzyme has not been investigated for its inhibition with any class of CA inhibitors. Here, we show that CynT2 was strongly inhibited by some substituted benzene-sulfonamides and the clinically used inhibitor sulpiride (K<sub>I</sub>s in the range of 82–97 nM). This study may be relevant for identifying novel CA inhibitors, as well as for another essential part of the drug discovery pipeline, such as the structure–activity relationship for this class of enzyme inhibitors. |
topic |
carbonic anhydrase sulfonamides inhibitors antibacterials <i>Escherichia coli</i> stopped-flow assay |
url |
https://www.mdpi.com/1422-0067/21/11/4175 |
work_keys_str_mv |
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