Studies On Alkaloids From Aconitum Franchetii Var. Villosulum

Diterpenoid alkaloids are a kind of complex natural products, enriched in the Ranunculaceae Aconitum,Delphinium,Consolida species and Rosaceae Spiraea species. These compounds have a wide range of pharmacological activities can be used in anti-inflammatory, analgesic, anti-cancer, cardiac, anti-Alzheimer’s disease etc.and because of its strong toxicity is also used as a new type of insecticide drugs used in modern agriculture. Aconitum franchetii var. villosulum is a variation of Aconitum franchetii Finet et Gagnep that has never been studied, distributed in western Sichuan China, growing at an altitude of 3400-4000 meters between the mountain slope or forest. For better develop and use of aconite medicinal resources, this paper takes Aconitum franchetii var. villosulum as the research object, the diterpenoid alkaloid constituents were studied systematically.In this paper, we used acid extraction and alkali precipitation to gain gross alkaloids, then used many separation methods like column chromatography and recrystallization, 20 diterpenoid alkaloids were obtained. Three new aconitine-type diterpenoid alkaloids, villosutine、villosudine and villosunine were isolated from the whole plant of Aconitum franchetii var. villosulum, together with 10 other known aconitine-type diterpenoid alkaloids: indaconitine、chasmaconitine、leucanthumsine A、chasmathnine、talatisamine、6-epichasmanine、ezochasmanine、pseudoaconitine、ezochasmaconitine、ludaconitine、1 known pyro-type diterpenoid alkaloid mithaconitine and 6 known franchetine-type diterpenoid alkaloids: franchetine、4-debenzoylfranchetine、leueandine、kongboendine.13-hydroxyfranchetine、vilmorisine. Their structures were elucidated on the basis of extensive spectroscopic analysis, including HR-ESI-MS, 1D and 2D NMR experiments.The anti-cancer activity of 15 compounds was determined by MTT assay. The results showed that compound leueandine (17) has an inhibitory effect on both MCF-7 breast cancer cells and HepG2 hepatoma cells. Molecular docking results showed that villosutine (1) and villosunine (3) were able to bind to ATP binding sites in DPOLB.Such compounds are inferred to produce anticancer effects by inhibiting the activity of DPOLB in cancer cells, block DNA repair and inhibit cell proliferation.