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Carbonic Anhydrase Inhibitors as Novel Drugs against Mycobacterial β-Carbonic Anhydrases: An Update on In Vitro and In Vivo Studies

Mycobacteria cause a variety of diseases, such as tuberculosis, leprosy, and opportunistic diseases in immunocompromised people. The treatment of these diseases is problematic, necessitating the development of novel treatment strategies. Recently, β-carbonic anhydrases (β-CAs) have emerged as potent...

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Autores principales: Aspatwar, Ashok, Winum, Jean-Yves, Carta, Fabrizio, Supuran, Claudiu T., Hammaren, Milka, Parikka, Mataleena, Parkkila, Seppo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278287/
https://www.ncbi.nlm.nih.gov/pubmed/30413024
http://dx.doi.org/10.3390/molecules23112911
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author Aspatwar, Ashok
Winum, Jean-Yves
Carta, Fabrizio
Supuran, Claudiu T.
Hammaren, Milka
Parikka, Mataleena
Parkkila, Seppo
author_facet Aspatwar, Ashok
Winum, Jean-Yves
Carta, Fabrizio
Supuran, Claudiu T.
Hammaren, Milka
Parikka, Mataleena
Parkkila, Seppo
author_sort Aspatwar, Ashok
collection PubMed
description Mycobacteria cause a variety of diseases, such as tuberculosis, leprosy, and opportunistic diseases in immunocompromised people. The treatment of these diseases is problematic, necessitating the development of novel treatment strategies. Recently, β-carbonic anhydrases (β-CAs) have emerged as potential drug targets in mycobacteria. The genomes of mycobacteria encode for three β-CAs that have been cloned and characterized from Mycobacterium tuberculosis (Mtb) and the crystal structures of two of the enzymes have been determined. Different classes of inhibitor molecules against Mtb β-CAs have subsequently been designed and have been shown to inhibit these mycobacterial enzymes in vitro. The inhibition of these centrally important mycobacterial enzymes leads to reduced growth of mycobacteria, lower virulence, and impaired biofilm formation. Thus, the inhibition of β-CAs could be a novel approach for developing drugs against the severe diseases caused by pathogenic mycobacteria. In the present article, we review the data related to in vitro and in vivo inhibition studies in the field.
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spelling pubmed-62782872018-12-13 Carbonic Anhydrase Inhibitors as Novel Drugs against Mycobacterial β-Carbonic Anhydrases: An Update on In Vitro and In Vivo Studies Aspatwar, Ashok Winum, Jean-Yves Carta, Fabrizio Supuran, Claudiu T. Hammaren, Milka Parikka, Mataleena Parkkila, Seppo Molecules Review Mycobacteria cause a variety of diseases, such as tuberculosis, leprosy, and opportunistic diseases in immunocompromised people. The treatment of these diseases is problematic, necessitating the development of novel treatment strategies. Recently, β-carbonic anhydrases (β-CAs) have emerged as potential drug targets in mycobacteria. The genomes of mycobacteria encode for three β-CAs that have been cloned and characterized from Mycobacterium tuberculosis (Mtb) and the crystal structures of two of the enzymes have been determined. Different classes of inhibitor molecules against Mtb β-CAs have subsequently been designed and have been shown to inhibit these mycobacterial enzymes in vitro. The inhibition of these centrally important mycobacterial enzymes leads to reduced growth of mycobacteria, lower virulence, and impaired biofilm formation. Thus, the inhibition of β-CAs could be a novel approach for developing drugs against the severe diseases caused by pathogenic mycobacteria. In the present article, we review the data related to in vitro and in vivo inhibition studies in the field. MDPI 2018-11-08 /pmc/articles/PMC6278287/ /pubmed/30413024 http://dx.doi.org/10.3390/molecules23112911 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Aspatwar, Ashok
Winum, Jean-Yves
Carta, Fabrizio
Supuran, Claudiu T.
Hammaren, Milka
Parikka, Mataleena
Parkkila, Seppo
Carbonic Anhydrase Inhibitors as Novel Drugs against Mycobacterial β-Carbonic Anhydrases: An Update on In Vitro and In Vivo Studies
title Carbonic Anhydrase Inhibitors as Novel Drugs against Mycobacterial β-Carbonic Anhydrases: An Update on In Vitro and In Vivo Studies
title_full Carbonic Anhydrase Inhibitors as Novel Drugs against Mycobacterial β-Carbonic Anhydrases: An Update on In Vitro and In Vivo Studies
title_fullStr Carbonic Anhydrase Inhibitors as Novel Drugs against Mycobacterial β-Carbonic Anhydrases: An Update on In Vitro and In Vivo Studies
title_full_unstemmed Carbonic Anhydrase Inhibitors as Novel Drugs against Mycobacterial β-Carbonic Anhydrases: An Update on In Vitro and In Vivo Studies
title_short Carbonic Anhydrase Inhibitors as Novel Drugs against Mycobacterial β-Carbonic Anhydrases: An Update on In Vitro and In Vivo Studies
title_sort carbonic anhydrase inhibitors as novel drugs against mycobacterial β-carbonic anhydrases: an update on in vitro and in vivo studies
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278287/
https://www.ncbi.nlm.nih.gov/pubmed/30413024
http://dx.doi.org/10.3390/molecules23112911
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