Inhibition of the β-carbonic anhydrase from the protozoan pathogen Trichomonas vaginalis with sulphonamides
Sulphonamides and their isosteres are classical inhibitors of the carbonic anhydrase (CAs, EC 4.2.1.1) metalloenzymes. The protozoan pathogen Trichomonas vaginalis encodes two such enzymes belonging to the β-class, TvaCA1 and TvaCA2. Here we report the first sulphonamide inhibition study of TvaCA1,...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2021-01-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/14756366.2020.1863958 |
| _version_ | 1818332566891003904 |
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| author | Linda J. Urbański Andrea Angeli Vesa P. Hytönen Anna Di Fiore Giuseppina De Simone Seppo Parkkila Claudiu T. Supuran |
| author_facet | Linda J. Urbański Andrea Angeli Vesa P. Hytönen Anna Di Fiore Giuseppina De Simone Seppo Parkkila Claudiu T. Supuran |
| author_sort | Linda J. Urbański |
| collection | DOAJ |
| description | Sulphonamides and their isosteres are classical inhibitors of the carbonic anhydrase (CAs, EC 4.2.1.1) metalloenzymes. The protozoan pathogen Trichomonas vaginalis encodes two such enzymes belonging to the β-class, TvaCA1 and TvaCA2. Here we report the first sulphonamide inhibition study of TvaCA1, with a series of simple aromatic/heterocyclic primary sulphonamides as well as with clinically approved/investigational drugs for a range of pathologies (diuretics, antiglaucoma, antiepileptic, antiobesity, and antitumor drugs). TvaCA1 was effectively inhibited by acetazolamide and ethoxzolamide, with KIs of 391 and 283 nM, respectively, whereas many other simple or clinically used sulphonamides were micromolar inhibitors or did not efficiently inhibit the enzyme. Finding more effective TvaCA1 inhibitors may constitute an innovative approach for fighting trichomoniasis, a sexually transmitted infection, caused by T. vaginalis. |
| first_indexed | 2024-12-13T13:37:47Z |
| format | Article |
| id | doaj.art-6382fcd128d643108745f96bff22092a |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-12-13T13:37:47Z |
| publishDate | 2021-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-6382fcd128d643108745f96bff22092a2022-12-21T23:43:41ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742021-01-0136133033510.1080/14756366.2020.18639581863958Inhibition of the β-carbonic anhydrase from the protozoan pathogen Trichomonas vaginalis with sulphonamidesLinda J. Urbański0Andrea Angeli1Vesa P. Hytönen2Anna Di Fiore3Giuseppina De Simone4Seppo Parkkila5Claudiu T. Supuran6Faculty of Medicine and Health Technology, Tampere UniversityNeurofarba Department, Sezione di Chimica Farmaceutica e Nutraceutica, Università degli Studi di FirenzeFaculty of Medicine and Health Technology, Tampere UniversityInstitute of Biostructures and Bioimaging of the National Research CouncilInstitute of Biostructures and Bioimaging of the National Research CouncilFaculty of Medicine and Health Technology, Tampere UniversityNeurofarba Department, Sezione di Chimica Farmaceutica e Nutraceutica, Università degli Studi di FirenzeSulphonamides and their isosteres are classical inhibitors of the carbonic anhydrase (CAs, EC 4.2.1.1) metalloenzymes. The protozoan pathogen Trichomonas vaginalis encodes two such enzymes belonging to the β-class, TvaCA1 and TvaCA2. Here we report the first sulphonamide inhibition study of TvaCA1, with a series of simple aromatic/heterocyclic primary sulphonamides as well as with clinically approved/investigational drugs for a range of pathologies (diuretics, antiglaucoma, antiepileptic, antiobesity, and antitumor drugs). TvaCA1 was effectively inhibited by acetazolamide and ethoxzolamide, with KIs of 391 and 283 nM, respectively, whereas many other simple or clinically used sulphonamides were micromolar inhibitors or did not efficiently inhibit the enzyme. Finding more effective TvaCA1 inhibitors may constitute an innovative approach for fighting trichomoniasis, a sexually transmitted infection, caused by T. vaginalis.http://dx.doi.org/10.1080/14756366.2020.1863958carbonic anhydrasesulphonamideinhibitortrichomonas vaginalistrichomoniasis |
| spellingShingle | Linda J. Urbański Andrea Angeli Vesa P. Hytönen Anna Di Fiore Giuseppina De Simone Seppo Parkkila Claudiu T. Supuran Inhibition of the β-carbonic anhydrase from the protozoan pathogen Trichomonas vaginalis with sulphonamides Journal of Enzyme Inhibition and Medicinal Chemistry carbonic anhydrase sulphonamide inhibitor trichomonas vaginalis trichomoniasis |
| title | Inhibition of the β-carbonic anhydrase from the protozoan pathogen Trichomonas vaginalis with sulphonamides |
| title_full | Inhibition of the β-carbonic anhydrase from the protozoan pathogen Trichomonas vaginalis with sulphonamides |
| title_fullStr | Inhibition of the β-carbonic anhydrase from the protozoan pathogen Trichomonas vaginalis with sulphonamides |
| title_full_unstemmed | Inhibition of the β-carbonic anhydrase from the protozoan pathogen Trichomonas vaginalis with sulphonamides |
| title_short | Inhibition of the β-carbonic anhydrase from the protozoan pathogen Trichomonas vaginalis with sulphonamides |
| title_sort | inhibition of the β carbonic anhydrase from the protozoan pathogen trichomonas vaginalis with sulphonamides |
| topic | carbonic anhydrase sulphonamide inhibitor trichomonas vaginalis trichomoniasis |
| url | http://dx.doi.org/10.1080/14756366.2020.1863958 |
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