Isolation,Identification,Characterization Of Anticancer Compounds From Thevetia Peruviana Seeds And Chemical Engineering Of Related Compounds

Cardiac glycosides demonstrated definite anticancer efficiency,which are used in clinic for the treatment of heart diseases.Some cardiac glycoside extracts and their chemical derivatives are in clinical trial approved by FDA.However,elucidating their mechanisms of action and reducing cardiotoxity are crucial for their application in clinic for the treatment of cancer.Here,we first study the anticancer bioactive cardiac glycosides from the seeds of Thevetia Peruviana.40 cardiac glycosides including 17 new compounds were obtained from the extract of the seeds of Thevetia Peruviana by using various chromatographic methods including silica gel,sephadex LH-20,ODS column chromatography and reversed-phase high performance liquid chromatography(RP HPLC).Their chemical structures were characterized by various spectropic methods,including mass spectrometry(MS),nuclear magnetic resonance(NMR)and chemical methods.Meanwhile,we evaluated their inhibiting effects on activity,cell proliferation,induction of cancer cell apoptosis,and cell cycle arrest.In addition,based on our previous studies,we selected two cardiac glycosides,namelyβ-antiarin/α-antiarin,and labeled them with biotin.16 biotinylated cardiac glycoside chemical probes were synthesized with a mixture of trance and cis epimers.Their structures were characterized by the ESI-MS,1D-,and 2D-NMR spectra.Meanwhile,their induction of Nur77 protein expression and inhibition of cancer cell proliferation were evaluated.This study has enriched the chemical diversity of natural derived cardiac glycosides,and cardiac glycosides with stronger anticancer activity were also obtained.The preliminary mechanism of action of cardiac glycosides against cancer is also studied,which is helpful for the further study.Moreover,the biotinylated cardiac glycoside chemical probes have laid a solid foundation for fishing of target proteins interacted with cardiac glycosides.