Mitrephorines A–E and Other Cytotoxic Aporphinoids from the Bark of <i>Mitrephora tomentosa</i>

Six previously undescribed alkaloids, including three dimeric aporphine alkaloids, mitrephorines A-C (<b>1</b>-<b>3</b>), two aristolactam-aporphine alkaloids, mitrephorines D and E (<b>4</b> and <b>5</b>), and one 4,5-dioxoaporphine alkaloid, 8-methoxycepharadione A (<b>6</b>), accompanied by 13 previously identified compounds, were isolated from the bark of <i>Mitrephora tomentosa</i>. Their structures were determined by the analysis of UV, IR, NMR, and HRMS, while absolute configurations were assigned by chiral HPLC, specific rotation values, and ECD spectral data. Known compounds (<b>7</b>-<b>19</b>) were identified by comparison with literature data. The structure of mitrephorine A was verified by the analysis of single-crystal X-ray diffraction. Alkaloid dimers were isolated as mixtures of enantiomers (<b>1</b>-<b>3</b>) and atropisomers (<b>4</b> and <b>5</b>). Several isolates were evaluated against HuCCA-1, MOLT-3, HeLa, HepG2, T47-D, MDA-MB-231, S102, H69AR, HL-60, and A549 cancer cell lines, as well as the MRC-5 normal cell line. Compound <b>11</b> was active against MOLT-3 and HeLa cancer cell lines with respective IC₅₀ values of 4.5 and 5.1 μM, while compound <b>12</b> exhibited cytotoxicity against HuCCA-1 and MOLT-3 cancer cell lines (IC₅₀ values of 10.0 and 7.9 μM, respectively). None of the isolates were toxic against the MRC-5 normal cell line, with doxorubicin hydrochloride serving as the positive control.