Studies On Steroids And Cytotoxicity Of The Leaves Of Nerium Indicum. Mill

This dissertation consisted of three chapters:Chapter one was the advances of the studies on the plant of Nerium indicum. Mill. Chapter two was study on steroids of the leaves Nerium indicum plant. Chapter three was the cytotoxicity evaluation and SAR discussion of compounds isolated from the leaves of Nerium indicum. Mill.Nerium indicum. Mill(Nerium oleander L) is Apocynaceae, a rare evergreen shrub. It includes many chemical constituents, such as cardiac glycosides, pregnanes, terpenes and flavonoids etc.. The plant which has been reputed as therapeutic agents, has varieties of biological activities including heart failure, cancer, anti-neoplastic, anti-inflammatory, sedation, anti-bacterial and anthelminthic effects.Phytochemical studies on Nerium indicum. Mill have led to the isolation fourteen compounds, including one new pregnane,14α,16-dihydroxy-3-oxo-γ-lactone-pregn-4-en-21-oic acid (16β,17α) (JZT-27), and thirteen known cardiac glycosides:oleandrin (JZT-2), oleandrigenin (JZT-3), neriosid (JZT-4), nerigoside (JZT-5),16,17-didehydrosomalin (JZT-6), oleaside A (JZT-8), adynerin (JZT-9), odoroside-A (JZT-14),3β-hydroxy-5β-carda-8β,14β,20,(22)-trienolid (JZT-17), odoroside H (JZT-19), deacetyloandrin (JZT-21), adynerigenin (JZT-25),3β-hydroxy-5α-8β,14β-epoxy-card-20(22)-enolid (JZT-28) were isolated and indentified by comparison of their physical and spectral data with those reported in the literature.All the isolated compounds were tested for the cytotoxic activity against HeLa cell. Most of them exhibited strong cytotocity and JZT-14 had the strongest cytotoxicity with IC50 9.7 nM. Their structure-activity relationships were discussed. Cis A/B ring of cardiac aglycones is stronger than trans; cis C/D ring has strong cytotoxicity, trans or unsaturated C/D ring has no cytotoxicities; the hydroxyl or acetyl substituted at C16 do not change their cytotoxicities; the double bond between C16 and C17 heavily decreased their cytotoxicities; and 3-O-glycosidization significantly increase their cytotoxicities.