Structurally diverse flavonoids from Selaginella doederleinii and their biological activity against laryngeal cancer

Ten previously undescribed flavonoids, seladoeflavones J˗Q, C, and E (1˗10), together with fifteen known biflavones (11-25), have been isolated from Selaginella doederleinii (the whole herbs). The structures of the new compounds were determined using 1D and 2D NMR as well as MS data. Comparing the experimental spectral data and NMR calculations, we determined the structures of compounds 1-5, 7, and 8. Comparing the circular dichroism (CD) values of compounds 5-10 with the reported data, we confirmed their absolute stereochemistries. The originally proposed structures of seladoeflavones C and E were corrected to be the same as those of compounds 7 and 8 in the article. All compounds were assessed for cytotoxic effects in diverse cancer cells. Most notably, 2'',3''-Dihydroochnaflavone (14) and Involvenflavone G (19) showed significant anti-proliferation and pro-apoptotic effects in laryngeal cancer cells (Hep-2 and FaDu). Moreover, mechanistic studies have identified that compound 14 induced apoptosis by suppressing the Akt/mTOR signaling pathway. In addition, compound 19 downregulated endoplasmic reticulum (ER) stress pathways. This study found that compounds 14 and 19 show good potential as anti-laryngeal cancer agents, which provides strong evidence for using S. doederleinii as an effective treatment for laryngeal cancer.