Octahydro-Protoberberine and Protoemetine-Type Alkaloids from the Stems of <i>Alangium salviifolium</i> and Their Cytotoxicity

Two octahydro-protoberberine alkaloids, alangiifoliumines A (<b>1</b>) and B (<b>2</b>), and two new protoemetine derivatives, alangiifoliumines C (<b>3</b>) and D (<b>4</b>), together with 11 known compounds, have been isolated from the stems of <i>Alangium salviifolium</i>. 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 <b>1</b> and <b>2</b> 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 <b>1</b>, <b>3</b>, and <b>6</b>–<b>14</b> exhibited inhibitory effects against all three human cancer cell lines, with half-maximal inhibitory concentration (IC₅₀) values in the range of 3 nM to 9.4 μM.