Lepicarpines A and B from the leaves of Ficus lepicarpa

Two new phenanthroindolizidine alkaloids, lepicarpine A ( 1 ) and lepicarpine B ( 2 ), along with two known compounds, (+)-6-demethyltylocrebrine ( 3 ) and (+)-6-demethyltylophorine ( 4 ), were isolated from the leaves of Ficus lepicarpa . Their chemical structures and absolute configurations were elucidated through comprehensive spectroscopic analyses. In vitro cytotoxicity assays revealed that all four compounds exhibited antiproliferative activity against human cancer cell lines. Compound 1 showed pronounced selectivity toward colorectal adenocarcinoma SW48 cells (IC 50 0.66 μM), demonstrating 10-fold greater potency than 5-fluorouracil. Notably, compound 2 exhibited the most potent and broad-spectrum cytotoxic activity, with IC 50 values of 0.05 μM (SW48), 0.64 μM (Caco-2), and 0.17 μM (H1299), achieving potency comparable to doxorubicin against SW48 cells and significantly surpassing 5-fluorouracil across all tested cell lines. The occurrence of phenanthroindolizidine alkaloids in F. lepicarpa further supports their chemotaxonomic association with Section Sycocarpus of Subgenus Sycomorus . • Two new phenanthroindolizidine alkaloids were isolated from Ficus lepicarpa • Lepicarpine B showed exceptional cytotoxicity (IC 50 0.05 μM) against SW48 cells. • The occurrence of phenanthroindolizidines supports Section Sycocarpus affiliation.