New hormonemate derivatives from the endophytic fungus Dothiora sp.

Arid zones in Andalucía have special edaphological and climatic conditions such as low rainfall, high sunshine levels and specific lithology where loamy materials and evaporites abound. Native plant communities from these arid zones possess distinctive survival characteristics in these special conditions, which have led to the existence of a high degree of endemic plants with highly adapted endophyte ecosystems poorly studied. It is precisely this singularity which turns them into a valuable potential source for the isolation of new unique host-specific endophytes. Fungal endophytes are known to produce a wide variety of secondary metabolites involved in their adaptation and survival within higher plants.

Launaea arborescens was collected in Tabernas desert (Andalucía, Spain), an arid area of the Almería province, being one of the representative plants characteristic of this geographic region. The fungal strain Dothiora sp. was isolated from this plant and the taxonomic determination of its genus and species was performed by sequencing the complete ITS1 – 5.8S-ITS2 – 28S region or independent ITS and 28S rDNA compared with GenBank and the NITE Biological Resource Center databases by using the BLAST application [1]. Acetone extract from the strain grown in the YES medium showed cytotoxicity against 2 cancer cell lines: human breast adenocarcinoma (MCF-7) and liver carninoma (HEPG2). Bioassay-guided fractionation of this extract using SP207ss resin column chromatography and preparative reversed-phased HPLC led to the isolation of six new natural products, hormonemates B-G, structurally related to hormonemate [2] whose chemical characterization is reported herein for the first time. Cytotoxic activities of the pure compounds against human liver carcinoma (HEPG2), breast (MCF-7) and pancreatic carcinoma (MiaPaca) were determined. Moderate cytotoxicity in the micromolar range was found for four of these compounds against the HEPG2 (IC₅₀ = 26 – 36µM) and MCF-7 (IC₅₀ = 11 – 28µM) cell lines.

Acknowledgements: To the Junta de Andalucía for financial support through the Project RNM-7987.

Keywords: Launaea arborescens, fungal endophytes, Dothiora sp., hormonemate, cytotoxicity.

References:

[1] González-Menéndez V, Pérez-Bonilla M, Pérez-Victoria I, Martín J, Muñoz F, Reyes F, Tormo JR, Genilloud O. Multicomponent Analysis of the Differential Induction of Secondary Metabolite Profiles in Fungal Endophytes. Molecules 2016; 21: 234 – 250

[2] Filip P, Weber RWS, Sterner O, Anke T. Hormonemate, a New Cytotoxic and Apoptosis-Inducing Compound from the Endophytic Fungus Hormonema dematioides. I. Identification of the Producing Strain, and Isolation and Biological Properties of Hormonemate. Z Naturforsch 2003; 58: 547 – 552

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