Cargando…

First total synthesis of chromanone A, preparation of related compounds and evaluation of their antifungal activity against Candida albicans, a biofilm forming agent

A straightforward and convenient approach for the first total syntheses of chromanone A and a related 7-OMe substituted natural product is reported. These unique C-3 substituted 2-hydroxymethyl chromones were recently isolated as fungal metabolites. Chromanone A was synthesized in 25.3% overall yiel...

Descripción completa

Detalles Bibliográficos
Autores principales: Cortés, Iván, Cordisco, Estefanía, Kaufman, Teodoro S., Sortino, Maximiliano A., Svetaz, Laura A., Bracca, Andrea B. J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9033609/
https://www.ncbi.nlm.nih.gov/pubmed/35479228
http://dx.doi.org/10.1039/d1ra02553h
_version_ 1784692932213735424
author Cortés, Iván
Cordisco, Estefanía
Kaufman, Teodoro S.
Sortino, Maximiliano A.
Svetaz, Laura A.
Bracca, Andrea B. J.
author_facet Cortés, Iván
Cordisco, Estefanía
Kaufman, Teodoro S.
Sortino, Maximiliano A.
Svetaz, Laura A.
Bracca, Andrea B. J.
author_sort Cortés, Iván
collection PubMed
description A straightforward and convenient approach for the first total syntheses of chromanone A and a related 7-OMe substituted natural product is reported. These unique C-3 substituted 2-hydroxymethyl chromones were recently isolated as fungal metabolites. Chromanone A was synthesized in 25.3% overall yield from the readily available pyrocatechol, whereas the second natural product was prepared in 39.7% global yield. A small library of chromones, including both natural products and some of their synthetic heterocyclic precursors, was evaluated against Candida albicans ATCC 10231, a biofilm forming agent. It was found that 8-methoxy-3-methyl-4-oxo-4H-chromene-2-carbaldehyde, a partially oxidized form of chromanone A, exhibited a minimum inhibitory concentration of 7.8 μg mL(−1) and significantly inhibited the yeast's virulence factors, including the adherence to buccal epithelial cells and the secretion of phospholipases, as well as the formation of germ tubes and the generation of the hyphal pseudomycelium. In addition, despite the heterocycle exhibiting non-significant inhibition of the formation of the Candida biofilm, it completely inhibited the growth of C. albicans in preformed biofilms at 62.5 μg mL(−1).
format Online
Article
Text
id pubmed-9033609
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher The Royal Society of Chemistry
record_format MEDLINE/PubMed
spelling pubmed-90336092022-04-26 First total synthesis of chromanone A, preparation of related compounds and evaluation of their antifungal activity against Candida albicans, a biofilm forming agent Cortés, Iván Cordisco, Estefanía Kaufman, Teodoro S. Sortino, Maximiliano A. Svetaz, Laura A. Bracca, Andrea B. J. RSC Adv Chemistry A straightforward and convenient approach for the first total syntheses of chromanone A and a related 7-OMe substituted natural product is reported. These unique C-3 substituted 2-hydroxymethyl chromones were recently isolated as fungal metabolites. Chromanone A was synthesized in 25.3% overall yield from the readily available pyrocatechol, whereas the second natural product was prepared in 39.7% global yield. A small library of chromones, including both natural products and some of their synthetic heterocyclic precursors, was evaluated against Candida albicans ATCC 10231, a biofilm forming agent. It was found that 8-methoxy-3-methyl-4-oxo-4H-chromene-2-carbaldehyde, a partially oxidized form of chromanone A, exhibited a minimum inhibitory concentration of 7.8 μg mL(−1) and significantly inhibited the yeast's virulence factors, including the adherence to buccal epithelial cells and the secretion of phospholipases, as well as the formation of germ tubes and the generation of the hyphal pseudomycelium. In addition, despite the heterocycle exhibiting non-significant inhibition of the formation of the Candida biofilm, it completely inhibited the growth of C. albicans in preformed biofilms at 62.5 μg mL(−1). The Royal Society of Chemistry 2021-06-01 /pmc/articles/PMC9033609/ /pubmed/35479228 http://dx.doi.org/10.1039/d1ra02553h Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/
spellingShingle Chemistry
Cortés, Iván
Cordisco, Estefanía
Kaufman, Teodoro S.
Sortino, Maximiliano A.
Svetaz, Laura A.
Bracca, Andrea B. J.
First total synthesis of chromanone A, preparation of related compounds and evaluation of their antifungal activity against Candida albicans, a biofilm forming agent
title First total synthesis of chromanone A, preparation of related compounds and evaluation of their antifungal activity against Candida albicans, a biofilm forming agent
title_full First total synthesis of chromanone A, preparation of related compounds and evaluation of their antifungal activity against Candida albicans, a biofilm forming agent
title_fullStr First total synthesis of chromanone A, preparation of related compounds and evaluation of their antifungal activity against Candida albicans, a biofilm forming agent
title_full_unstemmed First total synthesis of chromanone A, preparation of related compounds and evaluation of their antifungal activity against Candida albicans, a biofilm forming agent
title_short First total synthesis of chromanone A, preparation of related compounds and evaluation of their antifungal activity against Candida albicans, a biofilm forming agent
title_sort first total synthesis of chromanone a, preparation of related compounds and evaluation of their antifungal activity against candida albicans, a biofilm forming agent
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9033609/
https://www.ncbi.nlm.nih.gov/pubmed/35479228
http://dx.doi.org/10.1039/d1ra02553h
work_keys_str_mv AT cortesivan firsttotalsynthesisofchromanoneapreparationofrelatedcompoundsandevaluationoftheirantifungalactivityagainstcandidaalbicansabiofilmformingagent
AT cordiscoestefania firsttotalsynthesisofchromanoneapreparationofrelatedcompoundsandevaluationoftheirantifungalactivityagainstcandidaalbicansabiofilmformingagent
AT kaufmanteodoros firsttotalsynthesisofchromanoneapreparationofrelatedcompoundsandevaluationoftheirantifungalactivityagainstcandidaalbicansabiofilmformingagent
AT sortinomaximilianoa firsttotalsynthesisofchromanoneapreparationofrelatedcompoundsandevaluationoftheirantifungalactivityagainstcandidaalbicansabiofilmformingagent
AT svetazlauraa firsttotalsynthesisofchromanoneapreparationofrelatedcompoundsandevaluationoftheirantifungalactivityagainstcandidaalbicansabiofilmformingagent
AT braccaandreabj firsttotalsynthesisofchromanoneapreparationofrelatedcompoundsandevaluationoftheirantifungalactivityagainstcandidaalbicansabiofilmformingagent