Highly Fused Lindenane Sesquiterpenoid Dimers with Apoptosis-Inducing Properties from Chloranthus holostegius var....

Six undescribed lindenane sesquiterpenoid dimers (LSDs), shimianolides A-F (1-6), were isolated from the whole plants of Chloranthus holostegius var. shimianensis. Shimianolides A-C (1-3) represent an unprecedented class of LSDs, distinguished by a highly fused 3/5/6/6/6/5/6/6/5/3 decacyclic scaffold. All isolates were evaluated for their inhibitory effects on LPS-induced NO production in RAW264.7 macrophages and their cytotoxicity against five human cancer cell lines. Compound 4 exhibited moderate cytotoxicity against the HL-60 cell line with an IC₅₀ value of 15.6 ± 1.11 μM, comparable to that of the positive control cisplatin. Further investigation demonstrated that compound 4 induced apoptosis in HL-60 cells, with apoptosis rates of 36.9% at 15.0 μM and 47.5% at 30.0 μM. These results highlight the potential of LSDs as lead compounds for leukemia therapy.