Studies On The Discovery And Activity Of Alkaloids From Melodinus Magnificus Tsiang

The plants of the genus Melodinus（Apocynaceae）are mostly distributed in tropical Asia and Oceania to the Pacific coast,which comprises about 53 species.There are 11 species produced in China,which are distributed in Southwest China,South China and Taiwan.Plants of this genus are rich in alkaloids and have significant pharmacological activities,mainly including anti-tumor,anti-inflammatory,anti-bacterial and so on.As a unique plant in China,M.magnificus Tsiang has the effect of invigorating qi,eliminating accumulation and killing insects.In this study,the alkaloids of M.magnificus Tsiang and its anti-tumor activity were studied.The research object of this study is M.magnificus Tsiang.Firstly,silica gel column chromatography,sephadex gel column chromatography,reversed phase C18 column chromatography,HPLC and other methods were used to separate and purify the alkaloids of M.magnificus Tsiang to obtain the monomer compounds.Then the structures of the isolated monomer compounds were analyzed by modern spectral techniques such as ESI-MS and NMR.Finally,the antitumor activity of the isolated compounds was evaluated.In this study,19 compounds were isolated and identified from the M.magnificus Tsiang.Among them,there are 18 alkaloids:tabersonine（2）,11-methoxytabersonine（3）,Δ¹⁴-vincamenine（4）,lochnerinine（5）,voafrine B（6）,melodimagnifine A（7）,Δ¹⁴-vincanol（8）,scandine（9）,O-methyl-16-epi-Δ¹⁴-vincanol（10）,melodinhenine D（11）,tenuicausine（12）,19-epimeloscandonine（13）,meloscandonine（14）,16-epi-Δ¹⁴-vincamine（15）,19R-vindolinine（16）,19S-vindolinine（17）,Δ¹⁴-vincine（18）,Δ¹⁴-isoeburnamine（19）;One other type compound:2-ethylhexyl phthalate（1）.Compound7 is new compound.Compounds 1,3-6,8,10-13,15,16,18 and 19 are isolated from this plant for the first time.Compounds 2,3 and 5 belong to tabersonine-type alkaloids,compounds 4,8,10,15,18 and 19 belong to eburnamine-type alkaloids,and compounds 16 and 17 belong to vindolinine-type alkaloids.All of the above are monoterpene indole skeleton alkaloids.Compounds 9,11,13 and 14 are monoterpene quinoline alkaloids of scandine-type.Compounds 6,7,12 are bisindole alkaloids.The cytotoxic activity of the isolated monomer compounds was evaluated and screened by MTT assay.The results showed that compounds 2,3 and 5 had significant cytotoxic activity.Compound 3 showed the best inhibitory effect on Hep G2,with IC₅₀value of 0.018±0.09μM.Compound 5 showed strong cytotoxic activity against Hep G2,with IC₅₀ value of 0.84±0.80μM.The results suggested that the tabersonine-type alkaloids may be the main components exerting antitumor activity in M.magnificus Tsiang.In this thesis,the alkaloids of M.magnificus Tsiang were studied,which would provide theoretical basis for the exploitation and utilization of the plant.