Isolation and identification of Wnt inhibition-specific metabolites from an Amazonian palm tree endophyte Lasiodiplodia venezuelensis

The Wnt signaling pathway controls multiple events during embryonic development of multicellular animals of almost all taxa and, when aberrantly activated in the adult, is carcinogenic. Breast cancers are dependent on Wnt pathway overactivation mostly through dysregulation of pathway component proteins expression, which necessitates search of the therapeutically relevant compounds targeting them [1]. In the present work, the objective was to explore the chemical diversity and the presence of selective Wnt inhibitors within a unique collection of 54 fungi isolated as endophytes from the long-lived Amazonian understorey palm Astrocaryum sciophilum and also from its near environment. The fungi were cultured, extracted with ethyl acetate and screened for their effects on cell proliferation and in the Wnt pathway [2]. 13 extracts exhibited a specific Wnt inhibition activity, 6 of them being true endophytes of A. sciophilum. The endophytic strain Lasiodiplodia venezuelensis, was prioritised for scaled up fractionation for its selective activity and taxonomical originality. Application of geometric transfer from analytical HPLC conditions to semi preparative scale and use of dry load injection enable the isolation of 14 pure compounds in a single step [3]. The structural elucidation of these compounds were performed by conventional spectroscopic methods such as HRMS and 2D NMR. Among the molecules identified, 5 are original natural products described for the first time, and 9 are new to this species. Some of the isolated compounds are potent selective inhibitors of the Wnt pathway.

Acknowledgement

This work has benefited from a joint ANR-SNF grant (SECIL, ref ANR-15-CE21-0016, SNF N° 310030E-164289).

• References

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• 3 Queiroz EF. et al. Utility of Dry Load Injection for an Efficient Natural Products Isolation at the Semi-Preparative Chromatographic Scale. J Chromatogr A 2019; 19: 30310-3