Studies On Antitumor Activities Of The Triterpenoid Saponins From Lysimachia Foenum-graecum Hance

Lysimachia foenum-graecum hance belongs to the genus Lysimachia of the family Primulaceae.However,data from recent phylogenetic analyses suggested its relocation to the family Myrsinaceae.It is mainly distributed in Guangxi,Guangdong,Sichuan,Yunnan,Guizhou and Jiangxi provinces of China.The aerial parts of this plant have been used not only as a perfumery plant and an insect repellent,but also for the treatment of colds and headaches in traditional Chinese medicine.Previous phytochemical investigation of this species led to isolation of several triterpenoid saponins,flavonoids and volatile oil,with the activities of cytotoxic,antioxidant,antibacterial,etc.In this thesis,chemical studies on L.foenum-graecum were conducted by using various chromatographic techniques for the isolation of their chemical constituents and spectroscopic methods for the structural elucidation.As a result,21 oleanane-type triterpenoid saponins were isolated and identified from L.foenum-graecum,which can be divided into three types:13?,28-epoxy-oleanane(1-6,15-21),?12-oleanene(7-11),28,30-lactone-oleanane(12-14).Compounds 1-14 were new triterpenoid saponins.The assay of the antitumor activities of compounds 1-21 demonstrated that saponins with the aglycone cyclamiretin A(1,2,15-17,and 19)exhibited moderate cytotoxicity against all tested human cancer cell lines,with IC50 values of 9.28-24.52 ?M,while the other saponins(3-14,18,20,and 21)were inactive(IC50>50 ?M).Among the 13?,28-epoxyoleanan-30-al-type triterpenoid saponins and by comparing the cytotoxicity of 1 and 2 with 20 and 21,the results suggested that the hydroxy group at C-16 might have an effect on the activity.Simultaneously,the cytotoxic activities of compounds 1,2,15-17,and 19 were tested on drug-resistant lung cancer celllines(A549 and A549/CDDP,respectively).Compound 16 displayed moderate cytotoxicity against A549/CDDP,with an IC50 value of 8.74 ?M and a resistant factor(RF)of 0.9.This work enriched the diversity of triterpenoid saponins of the genus Lysimachia,and the bioassay results suggested that L.foenum-graecum might be a prospective species for the discovery of anticancer compounds,which provides a better development for the exploitation and utilization of L.foenum-graecum.