Studies On The Chemical Constituents Of Antitumor Alkaloids From Two Species Plants Of Apocynaceae

Tabersonine and its analogues are the representative components of aspidosperma type monoterpenoid indole alkaloids.Previous studies have found that such compounds have significant inhibitory activities on the proliferation of multi-drug resistant tumor cell lines.Further studies have found that such alkaloids play a role by binding to colchicine sites of multi-drug resistant tumor cell lines.In order to expand the structural diversity of these compounds,two species of Apocynaceae,Melodinus tenuicaudatus and Kopsia officinalis was selected and the constituents of alkaloid was studied systematically.The dissertation is comprised of three chapters,in which the chemical and bioactive constituents of two plants,Melodinus tenuicaudatus and Kopsia officinalis have been phytochemically studied.Besides,chapter III reviews the chemical constituents and related actives of monoterpene indole alkaloids in the Melodinus.All compounds were isolated by the reversed-phase silica gel column chromatography,Sephadex LH-20,MCI,high performance liquid chromatography,and structural identification were by the 1D or 2D nuclear magnetic resonance,mass spectrometry,infrared spectrum,ultraviolet-visible spectrum,electron circular dichroism and so on.Altogether,72monoterpene indole alkaloids including 8 new ones were isolated and identified from two plants.The 8 new compounds were classified as three bisindole alkaloids（1-3）,three aspidospermine type monoterpene alkaloids（4-6）,and two aspidofractinine type monoterpene alkaloids（50,51）.1.Chemical and Bioactive Constituents of M.tenuicaudatusThrough the systematic study on the dried branches and leaves of Melodinus tenuicaudatus,49 compounds were isolated,among which 6 were new compounds.The main types of the compounds were aspidospermine type,eburnane type and mersinines type alkaloids.The cytotoxicity activity of the new compounds and known compounds were studied,the new compounds（1-4）showed cytotoxic activity against five tumor cell lines（HL-60,SMMC-7721,A-549,MCF-7,SW-480）,which compound 4 was against human Leukemia cells（HL-60）showed specific cytotoxic activity（5.15m（44））;Known compounds（7,9,10,14）were against five tumor cell lines（A-549,MDA-MB-231,KB,KB-VIN,MCF-7）showed cytotoxic activity,which compound 10 and compound 14 showed significant cytotoxic activity against five tumor cell lines(IC₅₀ 0.5-2.2m（44）).Among them,compound 1is the first aspidosperma-meloscandonine type dimerized monoterpene indole alkaloid,and its constituent monomers are connected by a relatively rare newly introduced methylene unit;Compound 2 is the first discovered eburnamine-meloscandonine type dimerized monoterpene indole alkaloid;Compound 6 is an aspidosperma type alkaloid degraded by C-3 position.2.Chemical Constituents of K.officinalisThrough the systematic study on the fruits of Kopsia officinalis,23 compounds were isolated,including 2 new compounds,the main type which is the alkaloid of aspidofractinine type.3.Review-Monoterpenoid Indole Alkaloids of MelodinusThe chapter summarized the chemical compositions and activities of monoterpenoid indole alkaloids from Melodinus,which 204 natural occurring constituents were presented and 34 references were cited.