Title: Cytotoxic chromenes from the leaves of Mallotus apelta (Lour.) Müll.-Arg.: malloapelta B, structure-activity relationships and a cancer stem cell perspective
Authors: Nguyen Hoang Anh
Nguyen Xuan Nhiem
Nguyen Vu Ha Anh
Volume: 10
Issue: 8
Pages: 71-81
Publication Date: 2026/08/28
Abstract:
: Mallotus apelta (Lour.) Müll.-Arg. (Euphorbiaceae), known in Vietnam as "Bùm b?p", is a folk remedy for chronic hepatitis and enteritis and a productive source of cytotoxic benzopyrans, yet the antiproliferative spectrum of its best-known constituent, malloapelta B, has been characterised almost exclusively on ovarian carcinoma. Nineteen compounds were isolated from the leaves of M. apelta collected in Vinh Phuc Province, northern Vietnam, and their structures established by HR-ESI-MS together with 1D and 2D NMR; malloapelta B (MA14, C17H20O4) was obtained as a white amorphous powder (16.7 mg, 0.00033% w/w of dried leaves). All nineteen compounds were screened at 30 µM against PC-3 prostate and MCF-7 breast carcinoma cells, and the nine active compounds were then titrated against PC-3, MCF-7, HT-29 colorectal and TOV-21G ovarian carcinoma cells using the CCK-8 assay. Malloapelta B was the most potent compound on every line examined, with IC50 values of 1.24 ± 0.04 µM on MCF-7, 1.60 ± 0.05 µM on PC-3, 1.62 ± 0.09 µM on HT-29 and 1.72 ± 0.45 µM on TOV-21G, a strikingly flat, lineage-independent profile that exceeded the potency of capecitabine on PC-3 and HT-29 by seven- and eightfold. Activity segregated sharply by structural class: only compounds carrying a side-chain ?,?-unsaturated carbonyl were cytotoxic, whereas the saturated chromanes, flavonoid glycosides and megastigmane glycosides were inactive. Benchmarked against the reported IC50 of 12.71 µM on NTERA-2 embryonal carcinoma cells, malloapelta B is approximately eightfold less potent against a cancer stem cell model than against differentiated carcinoma cells, a gap that frames the principal challenge for developing this scaffold.