Anti-tumor metabolites from Synadenium grantii Hook F

Beta-sitosterol ( 1 ) and ingol 7,8,12-triacetate 3-phenylacetate ( 2 ) were isolated from leaves of Synadenium grantii Hook F. and screened for anti-tumor activity against a NCI 60 cell line panel. The highly functionalized ingol diterpene ( 2 ) displayed cytotoxicity against leukemia cancer cells (SR) and renal cancer cells (CAKI-1) with growth inhibition of 33% and 21%, respectively. Since PIK3α inhibitors are predicted to target PI3K/Akt signaling that is operative in renal cancer and leukemia, in silico molecular docking simulations with an alpha isoform of PIK3 were performed. Docking simulations confirmed that 2 fits in the active site with a docking score of −9.03 kcal/mol. Computational modeling included biological validation against the enzyme target, PI3KCα based on the commercial inhibitors X6K and GDC-0326 with experimental IC 50 values of 18 and 0.2 nM, respectively. Ingol diterpene ( 2 ), isolated from the medicinal herb S. grantii , holds potential as an inhibitor for select tumors; binding simulations indicate possible inhibition via the PI3K/Akt signaling pathway. Graphical abstract