Octahydro-Protoberberine and Protoemetine-Type Alkaloids from the Stems of Alangium salviifolium and Their Cytotoxicity.

Two octahydro-protoberberine alkaloids, alangiifoliumines A ( 1 ) and B ( 2 ), and two new protoemetine derivatives, alangiifoliumines C ( 3 ) and D ( 4 ), together with 11 known compounds, have been isolated from the stems of Alangium salviifolium . While the structures of these compounds were elucidated by spectroscopic methods, the absolute configurations of the new alkaloids were determined by conformational analysis and time-dependent density functional theory-electronic circular dichroism spectra calculations on selected stereoisomers. Compounds 1 and 2 represent the first 5,8,8a,9,12,12a,13,13a-octahydro-protoberberine derivatives, in which the aromatic ring D was reduced to cyclohexene. All the compounds isolated were evaluated for their cytotoxic activity against three human cancer cell lines: A-549, HeLa, and SKOV-3. Alkaloids 1 , 3 , and 6 - 14 exhibited inhibitory effects against all three human cancer cell lines, with half-maximal inhibitory concentration (IC ₅₀ ) values in the range of 3 nM to 9.4 μM.