Cytotoxic cardiac glycosides from the root of Streblus asper

Bioassay-guided separation of the root of Streblus asper led to the identification of six undescribed cardiac glycosides, including a rare cardiac glycoside dimer, along with twelve previously reported analogues. Their structures were determined on the basis of analyses of spectroscopic methods (1D and 2D-NMR spectroscopy), high-resolution electrospray ionization mass spectrometry (HRESIMS), circular dichroism (CD), and comparison of their spectroscopic data with previously reported data. Regarding their cytotoxic activities, microculture tetrazolium assays showed that all isolated cardiac glycosides strongly inhibited MCC-803, T24, SKOV-3, HepG2, Wi-38, and A549 cancer cell lines, with IC₅₀ values ranging from 0.075 μM to 0.752 μM. One cardiac glycoside, a rare cardiac glycoside dimer, exhibited the strongest activity against the six cancer cell lines, with IC₅₀ values ranging from 0.075 μM to 0.214 μM. In addition, the structure-activity relationships (SARs) of cardiac glycosides were investigated. In summary, S. asper showed marked cytotoxicity to several cancer cell lines, which could be meaningful for discovering new anticancer agents.