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Functionalization of the Chalcone Scaffold for the Discovery of Novel Lead Compounds Targeting Fungal Infections

The occurrence of invasive fungal infections represents a substantial threat to human health that is particularly serious in immunocompromised patients. The limited number of antifungal agents, devoid of unwanted toxic effects, has resulted in an increased demand for new drugs. Herein, the chalcone...

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Autores principales: Bonvicini, Francesca, Gentilomi, Giovanna A., Bressan, Francesca, Gobbi, Silvia, Rampa, Angela, Bisi, Alessandra, Belluti, Federica
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359675/
https://www.ncbi.nlm.nih.gov/pubmed/30669643
http://dx.doi.org/10.3390/molecules24020372
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author Bonvicini, Francesca
Gentilomi, Giovanna A.
Bressan, Francesca
Gobbi, Silvia
Rampa, Angela
Bisi, Alessandra
Belluti, Federica
author_facet Bonvicini, Francesca
Gentilomi, Giovanna A.
Bressan, Francesca
Gobbi, Silvia
Rampa, Angela
Bisi, Alessandra
Belluti, Federica
author_sort Bonvicini, Francesca
collection PubMed
description The occurrence of invasive fungal infections represents a substantial threat to human health that is particularly serious in immunocompromised patients. The limited number of antifungal agents, devoid of unwanted toxic effects, has resulted in an increased demand for new drugs. Herein, the chalcone framework was functionalized to develop new antifungal agents able to interfere with cell growth and with the infection process. Thus, a small library of chalcone-based analogues was evaluated in vitro against C. albicans ATCC 10231 and a number of compounds strongly inhibited yeast growth at non-cytotoxic concentrations. Among these, 5 and 7 interfered with the expression of two key virulence factors in C. albicans pathogenesis, namely, hyphae and biofilm formation, while 28 emerged as a potent and broad spectrum antifungal agent, enabling the inhibition of the tested Candida spp. and non-Candida species. Indeed, these compounds combine two modes of action by selectively interfering with growth and, as an added value, weakening microbial virulence. Overall, these compounds could be regarded as promising antifungal candidates worthy of deeper investigation. They also provide a chemical platform through which to perform an optimization process, addressed at improving potency and correcting liabilities.
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spelling pubmed-63596752019-02-06 Functionalization of the Chalcone Scaffold for the Discovery of Novel Lead Compounds Targeting Fungal Infections Bonvicini, Francesca Gentilomi, Giovanna A. Bressan, Francesca Gobbi, Silvia Rampa, Angela Bisi, Alessandra Belluti, Federica Molecules Article The occurrence of invasive fungal infections represents a substantial threat to human health that is particularly serious in immunocompromised patients. The limited number of antifungal agents, devoid of unwanted toxic effects, has resulted in an increased demand for new drugs. Herein, the chalcone framework was functionalized to develop new antifungal agents able to interfere with cell growth and with the infection process. Thus, a small library of chalcone-based analogues was evaluated in vitro against C. albicans ATCC 10231 and a number of compounds strongly inhibited yeast growth at non-cytotoxic concentrations. Among these, 5 and 7 interfered with the expression of two key virulence factors in C. albicans pathogenesis, namely, hyphae and biofilm formation, while 28 emerged as a potent and broad spectrum antifungal agent, enabling the inhibition of the tested Candida spp. and non-Candida species. Indeed, these compounds combine two modes of action by selectively interfering with growth and, as an added value, weakening microbial virulence. Overall, these compounds could be regarded as promising antifungal candidates worthy of deeper investigation. They also provide a chemical platform through which to perform an optimization process, addressed at improving potency and correcting liabilities. MDPI 2019-01-21 /pmc/articles/PMC6359675/ /pubmed/30669643 http://dx.doi.org/10.3390/molecules24020372 Text en © 2019 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 Article
Bonvicini, Francesca
Gentilomi, Giovanna A.
Bressan, Francesca
Gobbi, Silvia
Rampa, Angela
Bisi, Alessandra
Belluti, Federica
Functionalization of the Chalcone Scaffold for the Discovery of Novel Lead Compounds Targeting Fungal Infections
title Functionalization of the Chalcone Scaffold for the Discovery of Novel Lead Compounds Targeting Fungal Infections
title_full Functionalization of the Chalcone Scaffold for the Discovery of Novel Lead Compounds Targeting Fungal Infections
title_fullStr Functionalization of the Chalcone Scaffold for the Discovery of Novel Lead Compounds Targeting Fungal Infections
title_full_unstemmed Functionalization of the Chalcone Scaffold for the Discovery of Novel Lead Compounds Targeting Fungal Infections
title_short Functionalization of the Chalcone Scaffold for the Discovery of Novel Lead Compounds Targeting Fungal Infections
title_sort functionalization of the chalcone scaffold for the discovery of novel lead compounds targeting fungal infections
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359675/
https://www.ncbi.nlm.nih.gov/pubmed/30669643
http://dx.doi.org/10.3390/molecules24020372
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