Planta Med 2014; 80 - P1L40
DOI: 10.1055/s-0034-1394697

Search for anti-dengue secondary metabolites from Diospyros species and their endophytes

LA Peyrat 1, V Eparvier 1, J Letienne 2, C Eydoux 2, JC Guillemot 2, D Stien 1, M Litaudon 1
  • 1Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, CNRS, Avenue de la Terrasse, 91198 Gif sur Yvette Cedex, France
  • 2Centre de Recherche Architecture et Fonction des Macromolécules Biologiques, UMR7257 CNRS- Aix-Marseille Univ., 163, Avenue de Luminy, 13288 Marseille Cedex 09, France

Dengue fever is the most prevalent mosquito-borne viral disease of humans. In 50 years, the incidence of dengue has been multiplied by 30 and the WHO estimates the number of annual deaths caused by dengue at 22,000 [1]. Efforts to decrease transmission by vector control have failed, and no effective antiviral treatment is available. In 2009, a screening using a dengue replicon virus-cell-based assay [2] was performed on 3500 EtOAc extracts from 1500 plants. Among these extrats, 20 species of the genus Diospyros (Ebenaceae), distributed in tropical areas, showed significant inhibitory activity on dengue virus replication (Table 1). The aim of the study is to isolate and characterize active compounds from Diospyros species and/or their associated endophytes. Initially, metabolic proximity analysis was conducted from the UPLC-HRMS profiles of 33 plant extracts (similarity index in Table 1). The metabolic proximity is presented in the form of a dendrogram using the software MZmine 2 [4]. The results of this study showed that the chemical similarity is not related to the plant species or plant organs. Overall, metabolomic profiling allowed us to define large groups of extracts, both comprising active and inactive ones. Closely related profiles from active extract might indicate that the common major components of these extracts are responsible for the antiviral activity, while the comparison of chemically similar active and inactive extracts, will permit to find compounds of interest. For example, the only obvious difference between D. fasciculosa leaf extract and D. glans and D. vieillardii bark extracts is the presence of a peak at tR 23.50 min with m/z 499.3867 (MH+). This compound will be isolated and characterized in priority. To conclude, this methodology combining UPLC-HRMS and the data processing toolbox MZmine 2 proves to be a powerfull tool in dereplication.

Keywords: Ebenaceae, Diospyros, endophyte, dengue

References:

[1] Messina JP. et al. (2014) Trends in Microbiol. 22: 138 – 146.

[2] Massé N. et al. (2007) Virologie 2: 121 – 33.

[3] Arnold AE. et al. (2001) Mycol.Res 105(12): 1502 – 1507.

[4] Pluskal T. et al. (2010) BMC Bioinformatics 11: 395 – 406.