Dimeric guaianes from leaves of Xylopia vielana as snail inhibitors identified by high content screening

Abstract

The transcriptional repressor Snail trriggers epithelial-mesenchymal transition (EMT), the process allowing cancer cells with invasive and metastasis properties. In this study, we screened medicinal plants for the Snail inhibitory active components by high content screen (HCS) and found that the crude extract of Xylopia vielana leaves showed potential activity. Subsequently, bioassay-guided isolation of the extract of Xylopia vielana was performed to obtain twenty-four dimeric guaianes (1-24), including 16 new analogues (1-5, 8-11, 13-15, 17, 18, 21, and 22). Their structures were elucidated by the comprehensive application of multiple spectroscopic methods. Compounds 1, 11, 12, and 16 were initially identified as the active compounds. Wound healing assay, transwell migration assay and western blot experiments verified that compounds 1 and 12 inhibited the expression of Snail in a concentration-dependent manner, and compound 12 was verified as a potent tumor migration inhibitory agent. This work showed a practical strategy for the discovery of new Snail inhibitors from natural products and provided potential insights for dimeric guaianes as anticancer lead compounds specifically targeting Snail protein.

Keywords: Annonaceae; Dimeric guaianes; Snail inhibitors; Xylopia vielana.