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Synthesis of Trichodermin Derivatives and Their Antimicrobial and Cytotoxic Activities.


ABSTRACT: 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 IC50 values of 2 ?g/mL and were cytotoxic against tumorigenic cell line MCF-7 (breast carcinoma) and not against Fa2N4 (non-tumoral immortalized human hepatocytes).

SUBMITTER: Barua JE 

PROVIDER: S-EPMC6833013 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Synthesis of Trichodermin Derivatives and Their Antimicrobial and Cytotoxic Activities.

Barúa Javier E JE   de la Cruz Mercedes M   de Pedro Nuria N   Cautain Bastien B   Hermosa Rosa R   Cardoza Rosa E RE   Gutiérrez Santiago S   Monte Enrique E   Vicente Francisca F   Collado Isidro G IG  

Molecules (Basel, Switzerland) 20191022 20


Trichothecene mycotoxins are recognized as highly bioactive compounds that can be used in the design of new useful bioactive molecules. In <i>Trichoderma brevicompactum</i>, 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 <i>tri5</i> gene. Overexpression of <i>tri5</i> resulted in increased levels of trichodermin, a trichothecene-type toxin,  ...[more]

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