Fast and effective preparation of highly cytotoxic hybrid molecules of schweinfurthin E and OSW-1.

Abstract

Herein, we present the first synthesis of hybrid molecules combining the pharmacophores of two natural compounds, schweinfurthin E (SW-E) and the glycosidic moiety of OSW-1. These hybrids were designed leveraging the complementary binding of SW-E and OSW-1 to their biological target. The synthetic process highlights, in particular, one-pot functionalization and glycosylation of an L-arabinose unit using a D-xyloside donor and a CuAAC click reaction involving a polyfunctionalized prenylated stilbene derived from SW-E. The cytotoxicity of the four SW-E and OSW1 hybrids is also reported, two of them being much more cytotoxic than SW-E on a glioblastoma cancer cell line. Finally, a molecular modeling study is conducted to rationalize the biological results obtained.