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Synthesis of Trichodermin Derivatives and Their Antimicrobial and Cytotoxic Activities

Trichothecene mycotoxins are recognized as highly bioactive compounds that can be used in the design of new useful bioactive molecules. In Trichoderma brevicompactum, the first specific step in trichothecene biosynthesis is carried out by a terpene cyclase, trichodiene synthase, that catalyzes the c...

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Autores principales: Barúa, Javier E., de la Cruz, Mercedes, de Pedro, Nuria, Cautain, Bastien, Hermosa, Rosa, Cardoza, Rosa E., Gutiérrez, Santiago, Monte, Enrique, Vicente, Francisca, Collado, Isidro G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6833013/
https://www.ncbi.nlm.nih.gov/pubmed/31652666
http://dx.doi.org/10.3390/molecules24203811
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author Barúa, Javier E.
de la Cruz, Mercedes
de Pedro, Nuria
Cautain, Bastien
Hermosa, Rosa
Cardoza, Rosa E.
Gutiérrez, Santiago
Monte, Enrique
Vicente, Francisca
Collado, Isidro G.
author_facet Barúa, Javier E.
de la Cruz, Mercedes
de Pedro, Nuria
Cautain, Bastien
Hermosa, Rosa
Cardoza, Rosa E.
Gutiérrez, Santiago
Monte, Enrique
Vicente, Francisca
Collado, Isidro G.
author_sort Barúa, Javier E.
collection PubMed
description Trichothecene mycotoxins are recognized as highly bioactive compounds that can be used in the design of new useful bioactive molecules. In Trichoderma brevicompactum, the first specific step in trichothecene biosynthesis is carried out by a terpene cyclase, trichodiene synthase, that catalyzes the conversion of farnesyl diphosphate to trichodiene and is encoded by the tri5 gene. Overexpression of tri5 resulted in increased levels of trichodermin, a trichothecene-type toxin, which is a valuable tool in preparing new molecules with a trichothecene skeleton. In this work, we developed the hemisynthesis of trichodermin and trichodermol derivatives in order to evaluate their antimicrobial and cytotoxic activities and to study the chemo-modulation of their bioactivity. Some derivatives with a short chain at the C-4 position displayed selective antimicrobial activity against Candida albicans and they showed MIC values similar to those displayed by trichodermin. It is important to highlight the cytotoxic selectivity observed for compounds 9, 13, and 15, which presented average IC(50) values of 2 μg/mL and were cytotoxic against tumorigenic cell line MCF-7 (breast carcinoma) and not against Fa2N4 (non-tumoral immortalized human hepatocytes).
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spelling pubmed-68330132019-11-25 Synthesis of Trichodermin Derivatives and Their Antimicrobial and Cytotoxic Activities Barúa, Javier E. de la Cruz, Mercedes de Pedro, Nuria Cautain, Bastien Hermosa, Rosa Cardoza, Rosa E. Gutiérrez, Santiago Monte, Enrique Vicente, Francisca Collado, Isidro G. Molecules Article Trichothecene mycotoxins are recognized as highly bioactive compounds that can be used in the design of new useful bioactive molecules. In Trichoderma brevicompactum, the first specific step in trichothecene biosynthesis is carried out by a terpene cyclase, trichodiene synthase, that catalyzes the conversion of farnesyl diphosphate to trichodiene and is encoded by the tri5 gene. Overexpression of tri5 resulted in increased levels of trichodermin, a trichothecene-type toxin, which is a valuable tool in preparing new molecules with a trichothecene skeleton. In this work, we developed the hemisynthesis of trichodermin and trichodermol derivatives in order to evaluate their antimicrobial and cytotoxic activities and to study the chemo-modulation of their bioactivity. Some derivatives with a short chain at the C-4 position displayed selective antimicrobial activity against Candida albicans and they showed MIC values similar to those displayed by trichodermin. It is important to highlight the cytotoxic selectivity observed for compounds 9, 13, and 15, which presented average IC(50) values of 2 μg/mL and were cytotoxic against tumorigenic cell line MCF-7 (breast carcinoma) and not against Fa2N4 (non-tumoral immortalized human hepatocytes). MDPI 2019-10-22 /pmc/articles/PMC6833013/ /pubmed/31652666 http://dx.doi.org/10.3390/molecules24203811 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
Barúa, Javier E.
de la Cruz, Mercedes
de Pedro, Nuria
Cautain, Bastien
Hermosa, Rosa
Cardoza, Rosa E.
Gutiérrez, Santiago
Monte, Enrique
Vicente, Francisca
Collado, Isidro G.
Synthesis of Trichodermin Derivatives and Their Antimicrobial and Cytotoxic Activities
title Synthesis of Trichodermin Derivatives and Their Antimicrobial and Cytotoxic Activities
title_full Synthesis of Trichodermin Derivatives and Their Antimicrobial and Cytotoxic Activities
title_fullStr Synthesis of Trichodermin Derivatives and Their Antimicrobial and Cytotoxic Activities
title_full_unstemmed Synthesis of Trichodermin Derivatives and Their Antimicrobial and Cytotoxic Activities
title_short Synthesis of Trichodermin Derivatives and Their Antimicrobial and Cytotoxic Activities
title_sort synthesis of trichodermin derivatives and their antimicrobial and cytotoxic activities
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6833013/
https://www.ncbi.nlm.nih.gov/pubmed/31652666
http://dx.doi.org/10.3390/molecules24203811
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