Structurally diverse sesquiterpenes with anti-leukemia activity from the rare medicinal plant Liriodendron chinense.

A further phytochemical investigation on the branches and leaves of Liriodendron chinense, a rare medicinal and ornamental plant endemic to China, yielded thirty-four sesquiterpenes with diverse skeletons. The isolated compounds comprise 12 new naturally occurring sesquiterpenoids (1-12) and 22 known analogues (13-34). The new structures were elucidated by spectroscopic data analyses, and their absolute configurations (except for 10) were determined by electronic circular dichroism spectra, quantum-chemical calculations, and X-ray crystallography. Among them, liriochinolide A (1) is a rare chlorine-substituted germacrane-type sesquiterpenoid from the terrestrial plants. Bioassay evaluations revealed that most of the isolates exhibited remarkable cytotoxicity against three human leukemia cell lines (MV-4-11, HL-60 and Raji), with IC values ranging from 2.27 to 9.69 μM. Further exploration of anti-leukemia mechanism demonstrated that the bioactive compounds 5, 8, and 18 significantly induced the cell apoptosis, which was associated with down-regulation of the anti-apoptotic proteins BCL-2 and MCL-1.