RT Journal Article
T1 Synthesis of Trichodermin Derivatives and Their Antimicrobial and Cytotoxic Activities.
A1 Barúa, Javier E
A1 de la Cruz, Mercedes
A1 de Pedro, Nuria
A1 Cautain, Bastien
A1 Hermosa, Rosa
A1 Cardoza, Rosa E
A1 Gutiérrez, Santiago
A1 Monte, Enrique
A1 Vicente, Francisca
A1 Collado, Isidro G
K1 antimicrobial
K1 cytotoxic bioactivity
K1 sesquiterpenes
K1 synthesis
K1 tri genes
K1 trichothecene
AB 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 μg/mL and were cytotoxic against tumorigenic cell line MCF-7 (breast carcinoma) and not against Fa2N4 (non-tumoral immortalized human hepatocytes).
YR 2019
FD 2019-10-22
LK http://hdl.handle.net/10668/15355
UL http://hdl.handle.net/10668/15355
LA en
DS RISalud
RD Apr 14, 2025