Inhibitory Effects of Sulfonamide Derivatives on the β-Carbonic Anhydrase (MpaCA) from Malassezia pachydermatis, a Commensal, Pathogenic Fungus Present in Domestic Animals

Fungi are exposed to various environmental variables during their life cycle, including changes in CO2 concentration. CO2 has the potential to act as an activator of several cell signaling pathways. In fungi, the sensing of CO2 tri...

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Autores principales:	Viviana De Luca, Andrea Angeli, Valeria Mazzone, Claudia Adelfio, Fabrizio Carta, Silvia Selleri, Vincenzo Carginale, Andrea Scaloni, Claudiu T. Supuran, Clemente Capasso
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	carbonic anhydrase <i>Malassezia pachydermatis</i> CO<sub>2</sub> sensing sulfonamide inhibitors anti-dandruff antifungals Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/6b79f5fd7417448e88f9b82385c0fab6
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spelling	oai:doaj.org-article:6b79f5fd7417448e88f9b82385c0fab62021-11-25T17:58:13ZInhibitory Effects of Sulfonamide Derivatives on the <i>β</i>-Carbonic Anhydrase (MpaCA) from <i>Malassezia pachydermatis</i>, a Commensal, Pathogenic Fungus Present in Domestic Animals10.3390/ijms2222126011422-00671661-6596https://doaj.org/article/6b79f5fd7417448e88f9b82385c0fab62021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12601https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Fungi are exposed to various environmental variables during their life cycle, including changes in CO<sub>2</sub> concentration. CO<sub>2</sub> has the potential to act as an activator of several cell signaling pathways. In fungi, the sensing of CO<sub>2</sub> triggers cell differentiation and the biosynthesis of proteins involved in the metabolism and pathogenicity of these microorganisms. The molecular machineries involved in CO<sub>2</sub> sensing constitute a promising target for the development of antifungals. Carbonic anhydrases (CAs, EC 4.2.1.1) are crucial enzymes in the CO<sub>2</sub> sensing systems of fungi, because they catalyze the reversible hydration of CO<sub>2</sub> to proton and HCO<sub>3</sub><sup>-</sup>. Bicarbonate in turn boots a cascade of reactions triggering fungal pathogenicity and metabolism. Accordingly, CAs affect microorganism proliferation and may represent a potential therapeutic target against fungal infection. Here, the inhibition of the unique <i>β</i>-CA (MpaCA) encoded in the genome of <i>Malassezia pachydermatis</i>, a fungus with substantial relevance in veterinary and medical sciences, was investigated using a series of conventional CA inhibitors (CAIs), namely aromatic and heterocyclic sulfonamides. This study aimed to describe novel candidates that can kill this harmful fungus by inhibiting their CA, and thus lead to effective anti-dandruff and anti-seborrheic dermatitis agents. In this context, current antifungal compounds, such as the azoles and their derivatives, have been demonstrated to induce the selection of resistant fungal strains and lose therapeutic efficacy, which might be restored by the concomitant use of alternative compounds, such as the fungal CA inhibitors.Viviana De LucaAndrea AngeliValeria MazzoneClaudia AdelfioFabrizio CartaSilvia SelleriVincenzo CarginaleAndrea ScaloniClaudiu T. SupuranClemente CapassoMDPI AGarticlecarbonic anhydrase<i>Malassezia pachydermatis</i>CO<sub>2</sub> sensingsulfonamide inhibitorsanti-dandruffantifungalsBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12601, p 12601 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	carbonic anhydrase <i>Malassezia pachydermatis</i> CO<sub>2</sub> sensing sulfonamide inhibitors anti-dandruff antifungals Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	carbonic anhydrase <i>Malassezia pachydermatis</i> CO<sub>2</sub> sensing sulfonamide inhibitors anti-dandruff antifungals Biology (General) QH301-705.5 Chemistry QD1-999 Viviana De Luca Andrea Angeli Valeria Mazzone Claudia Adelfio Fabrizio Carta Silvia Selleri Vincenzo Carginale Andrea Scaloni Claudiu T. Supuran Clemente Capasso Inhibitory Effects of Sulfonamide Derivatives on the <i>β</i>-Carbonic Anhydrase (MpaCA) from <i>Malassezia pachydermatis</i>, a Commensal, Pathogenic Fungus Present in Domestic Animals
description	Fungi are exposed to various environmental variables during their life cycle, including changes in CO<sub>2</sub> concentration. CO<sub>2</sub> has the potential to act as an activator of several cell signaling pathways. In fungi, the sensing of CO<sub>2</sub> triggers cell differentiation and the biosynthesis of proteins involved in the metabolism and pathogenicity of these microorganisms. The molecular machineries involved in CO<sub>2</sub> sensing constitute a promising target for the development of antifungals. Carbonic anhydrases (CAs, EC 4.2.1.1) are crucial enzymes in the CO<sub>2</sub> sensing systems of fungi, because they catalyze the reversible hydration of CO<sub>2</sub> to proton and HCO<sub>3</sub><sup>-</sup>. Bicarbonate in turn boots a cascade of reactions triggering fungal pathogenicity and metabolism. Accordingly, CAs affect microorganism proliferation and may represent a potential therapeutic target against fungal infection. Here, the inhibition of the unique <i>β</i>-CA (MpaCA) encoded in the genome of <i>Malassezia pachydermatis</i>, a fungus with substantial relevance in veterinary and medical sciences, was investigated using a series of conventional CA inhibitors (CAIs), namely aromatic and heterocyclic sulfonamides. This study aimed to describe novel candidates that can kill this harmful fungus by inhibiting their CA, and thus lead to effective anti-dandruff and anti-seborrheic dermatitis agents. In this context, current antifungal compounds, such as the azoles and their derivatives, have been demonstrated to induce the selection of resistant fungal strains and lose therapeutic efficacy, which might be restored by the concomitant use of alternative compounds, such as the fungal CA inhibitors.
format	article
author	Viviana De Luca Andrea Angeli Valeria Mazzone Claudia Adelfio Fabrizio Carta Silvia Selleri Vincenzo Carginale Andrea Scaloni Claudiu T. Supuran Clemente Capasso
author_facet	Viviana De Luca Andrea Angeli Valeria Mazzone Claudia Adelfio Fabrizio Carta Silvia Selleri Vincenzo Carginale Andrea Scaloni Claudiu T. Supuran Clemente Capasso
author_sort	Viviana De Luca
title	Inhibitory Effects of Sulfonamide Derivatives on the <i>β</i>-Carbonic Anhydrase (MpaCA) from <i>Malassezia pachydermatis</i>, a Commensal, Pathogenic Fungus Present in Domestic Animals
title_short	Inhibitory Effects of Sulfonamide Derivatives on the <i>β</i>-Carbonic Anhydrase (MpaCA) from <i>Malassezia pachydermatis</i>, a Commensal, Pathogenic Fungus Present in Domestic Animals
title_full	Inhibitory Effects of Sulfonamide Derivatives on the <i>β</i>-Carbonic Anhydrase (MpaCA) from <i>Malassezia pachydermatis</i>, a Commensal, Pathogenic Fungus Present in Domestic Animals
title_fullStr	Inhibitory Effects of Sulfonamide Derivatives on the <i>β</i>-Carbonic Anhydrase (MpaCA) from <i>Malassezia pachydermatis</i>, a Commensal, Pathogenic Fungus Present in Domestic Animals
title_full_unstemmed	Inhibitory Effects of Sulfonamide Derivatives on the <i>β</i>-Carbonic Anhydrase (MpaCA) from <i>Malassezia pachydermatis</i>, a Commensal, Pathogenic Fungus Present in Domestic Animals
title_sort	inhibitory effects of sulfonamide derivatives on the <i>β</i>-carbonic anhydrase (mpaca) from <i>malassezia pachydermatis</i>, a commensal, pathogenic fungus present in domestic animals
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/6b79f5fd7417448e88f9b82385c0fab6
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Inhibitory Effects of Sulfonamide Derivatives on the <i>β</i>-Carbonic Anhydrase (MpaCA) from <i>Malassezia pachydermatis</i>, a Commensal, Pathogenic Fungus Present in Domestic Animals

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