Use of Botrytis cinerea enzymatic secretome to generate original phenylpropanoids derivatives having Wnt inhibition on triple negative breast cancer cells

The biotransformation of natural products using the Botrytis cinerea enzymatic secretome has proven to be an innovative and effective way to produce original derivatives [1]. Such reactions produce very complex compounds from simple natural product scaffolds, some of which have interesting biological activities. In the present work, the biotransformation of two 4-hydroxy-cinnamic acid derivatives was investigated. Caffeic acid and ferulic acid were successively incubated with the crude enzymatic extract (secretome) of B. cinerea. These biotransformations, were first carried out at the analytical scale for 24 hours. They were monitored by UHPLC-high resolution mass spectrometry (HRMS) to verify the complete transformation of starting substrates and the production of related derivatives. The reactions were then scaled-up with 200 mg of the starting compounds, controlled by HPLC-PDA-ELSD and purified by high-resolution semi-preparative HPLC. The same selectivity and a precise prediction of the separation between the analytical and semi-preparative scale were obtained using geometrical chromatography transfer methods [2]. The isolated compounds were fully characterized by NMR and HRMS. Using this approach eleven dimeric or trimeric phenylpropanoids analogues were obtained. Among these compounds, three are described here for the first time and some of them presented Wnt inhibition activities in breast cancer cells.

Fig.1

Acknowledgments

The authors are thankful to the Swiss National Science Foundation for providing financial support for this project (grant 205321_182438/1 E.F.Q. and K.G.). The School of Pharmaceutical Sciences of the University of Geneva (J.-L. Wolfender) is thankful to the Swiss National Science Foundation for the support in the acquisition of the NMR 600 MHz (SNF R’Equip Grant No. 316030_164095).

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