Investigation On Alklaoids From Tabernaemontana Corymbose And Their Anti-tumor Activity

In our previous study,vobasinyl-iboga-type bisindole alkaloids showed significant anti-tumor activity.Moreover,such alkaloids could affects the acidification of lysosome and impair its function,and thus induce the necrosis of tumor cells.Additionaly,such alkaloids are widely distributed in the genus Tabernaemontana.Herein,the alkaloid constituents of T.corymbosa?Apocynaceae?were systematically investigated?The branches and leaves of T.corymbosa were collected in December,2014,Menglun County of Yunnan Province,China?,and the antitumor activities of the new alkaloids were also evaluated.The reversed-phase silica gel column chromatography,MCI,Sephadex LH-20 and high-performance liquid chromatography were used for compounds isolation and nuclear magnetic resonance,mass spectrometry,infrared spectroscopy,electron circular dichroism,X-single crystal diffraction analysis,chemical conversion and quantum computational chemical methods were used for structural identification.Altogether,45 monoterpene alkaloids including 22 new ones were isolated and identified.The 22 new ones were classified as 16 vobasnyl-iboga type?Compound 1-16?and 6 monomeric alkaloids?4 iboga type indole alkaloids?26-29?,1 pentacylic type monoterpene alkaloid?30?and 1 vobasinyl-type?31??.Five human cancer cell lines?A-549,MCF-7,KB,KB-VIN,and MDA-MB-231?in SRB assay were used to evaluate their anti-proliferative activities by collaboration.The results indicated that most of the bisindole alkaloids except the monomers showed significant activities with IC₅₀ values range from 2.6 to 8.3?M.Among them,the hydroxylated stereocenter at C-3?compounds 1,1a,and 2?appears critical factor for their anti-proliferative activities.Moreover,the absolute configurations of the 19,20-oxirane ring and 16?-carbomethoxy group were also founded to be critical factors for their anti-proliferative activities within compounds 3 and 4.Last but not least,the chemical compositions and activities of monoterpenoid indole alkaloids dimers in plants are also reviewed in this thesis during the last 10 years?2006-2016?.