Siamenflavones A-C, three undescribed biflavonoids from Selaginella siamensis Hieron. and biflavonoids from spike mosses as EGFR inhibitor

Three undescribed biflavonoids (BFVs), siamenflavones A-C along with twelve BFVs were isolated from Selagi-nella siamensis Hieron. and Selaginella bryopteris (L.) Baker (Selaginellaceae). The chemical structures of unde-scribed compounds were established through comprehensive spectroscopic techniques, chemical correlations, and X-ray crystallography. The ten isolated BFVs, siamenflavones A-C, delicaflavone, chrysocauflavone, robustaflavone, robustaflavone-4-methylether, amentoflavone, tetrahydro-amentoflavone, and sciadopitysin were evaluated for the antiproliferative effects against four human cancer cell lines A549, H1975, HepG2 and T47D. Delicaflavone and robustaflavone 4 '-methylether exerted strong effects on the four human cancer cell lines. Siamenflavone B, delicaflavone and robustaflavone 4 '-methylether showed potent inhibitory activities against wild-type EGFR. The inhibition of the compounds was further supported by molecular docking and predictive intermolecular interactions. Molecular dynamics simulation studies of siamenflavone B and robus-taflavone-4 '-methylether complexed to EGFR-TK further supported inhibition of the compounds to the ATP binding site. Finally, analysis of pharmacokinetic and electronic properties using density-functional theory and known drug index calculations suggest that the compounds are pharmaceutically compatible for drug administration.