Synthesis and in vitro Anti-proliferative Activities on LNCaP, LS180 and MKN45 of Novel 20(R)-Panaxadiol Derivatives.

BACKGROUND: 20(R)-PD, a tetracyclic triterpenoid, is a non-natural saponin present in the form of protopanaxadiol. Because of its essential biological activities, especially anti-tumor activity, structural modification of 20(R)-PD and the development of innovative and novel 20(R)-PD derivatives with better anti-tumor activity are increasingly relevant. AIMS: 20(R)-Panaxadiol (20(R)-PD) can inhibit tumor proliferation. Three series of novel 20(R-PD derivatives were synthesized by modifying the A-ring. OBJECTIVE: The objective of this work was to synthesize and evaluate the in vitro anti-proliferative activities of 20(R)- PD derivatives in LNCaP, LS180, and MKN45 cancer cells. Structural modifications were performed at the C-3 position and A-ring. METHODS: The in vitro anti-proliferative activities of novel derivatives in LNCaP, LS180, and MKN45 cells were evaluated by the MTT assay. The effects of compounds 5 and C9 on apoptosis were determined by flow cytometry. RESULTS: Compounds 5, B2, C2, C4, C7, C8, C9, C10, and C11 exhibited good anti-proliferative activities in LNCaP, LS180, and MKN45 cells in vitro. The best anti-proliferative activity was observed for the C-series derivatives with the introduction of amino acids at the C-3 position. C9 exhibited good potent activity with an IC50 of 2.89 µM. CONCLUSION: Compound C9 is a potential candidate with potent anti-proliferative activity.

Cold-induced ginsenosides accumulation is associated with the alteration in DNA methylation and relative gene expression in perennial American ginseng (Panax quinquefolius L.) along with its plant growth and development process.

BACKGROUND: Ginsenosides accumulation responses to temperature are critical to quality formation in cold-dependent American ginseng. However, the studies on cold requirement mechanism relevant to ginsenosides have been limited in this species. METHODS: Two experiments were carried out: one was a multivariate linear regression analysis between the ginsenosides accumulation and the environmental conditions of American ginseng from different sites of China and the other was a synchronous determination of ginsenosides accumulation, overall DNA methylation, and relative gene expression in different tissues during different developmental stages of American ginseng after experiencing different cold exposure duration treatments. RESULTS: Results showed that the variation of the contents as well as the yields of total and individual ginsenosides Rg1, Re, and Rb1 in the roots were closely associated with environmental temperature conditions which implied that the cold environment plays a decisive role in the ginsenoside accumulation of American ginseng. Further results showed that there is a cyclically reversible dynamism between methylation and demethylation of DNA in the perennial American ginseng in response to temperature seasonality. And sufficient cold exposure duration in winter caused sufficient DNA demethylation in tender leaves in early spring and then accompanied the high expression of flowering gene PqFT in flowering stages and ginsenosides biosynthesis gene PqDDS in green berry stages successively, and finally, maximum ginsenosides accumulation occurred in the roots of American ginseng. CONCLUSION: We, therefore, hypothesized that cold-induced DNA methylation changes might regulate relative gene expression involving both plant development and plant secondary metabolites in such cold-dependent perennial plant species.