Study On The Structural Modification And Bioactivities Of Wedelia Prostrata,Chemical Constituents And Bioactivities Of Salvia Bowleyana Dunn

Objectives:With structural modification and chemical isolation of ent-kaurane diterpenoids from Wedelia prostrata and meliandiol from Melia azedarach L.,a series of natural compounds and their derivatives have been obtained.In order to get better antitumor compounds,we used MTT assays to screen anti-tumor activities for these compounds.Methods:?1?Synthetic methods:?a?Used ent-kaurane as starting material to introduce the efficacy of functional groups of?,?-unsaturated ketone.Then used the strategy to modify the carbanyl group at C-15 and carboxyl group at C-4.The imide group can be introduced to carbanyl group at C-15.Through these methods,a series of derivatives,such as W1-1^W1-10 were obtained.?b?Used meliandiol as starting material to oxidate C21-OH into a lactone,which improved its antitumor activity greatly.?2?Isolation methods:?a?Powdered Wedelia prostrata was extracted with MeOH three times.After evaporation of the solvent,the residue was suspended in H₂O and extracted with petroleum ether,AcOEt,and BuOH,then each layer undertook isolation and purification;?b?Methods include:silica gel column chromatography,Sephadex LH-20,MCI and HPLC etc.UV,IR,MS and NMR were used for identification of the structures of isolated compounds.?3?Activity test:Apply the methods of MTT to screen anti-tumor activity for the compounds which were obtained by synthesis and isolation.?4?Structure-activity relationship studying:We can summarize the structure-activity relationship by comparing the antitumor activity data.Results:?1?Used the above modifications and isolation methods,10 derivatives of ent-kaurane?W1-1^W1-10?,4 kaurane diterpenoid compounds?W1^W4?,3 derivatives of Meliandiol?M1-1^M1-3?,16 compounds?S1^S16?from the roots of Salvia bowleyana were obtained.All of the compounds were characterized by ¹H-NMR,¹³C-NMR,MS spectra.?2?From the antitumor activity data,it was showed that the activity of ent-kaurane derivatives were improved greatly than starting material W1 and some derivatives W1-1^W1-4 showed strong activity IC50 value between 0.31¹.14?g/mL for SW620,SGC-7901,and K562 cell lines.After oxidation of C-21-OH of Meliandiol into a lactone,the activity of Meliandiol derivative M1-1 was improved greatly.Conclusions:A series of derivatives of kaurenoic acid?W1?with 15-keto and amide groups or ester groups at C-4 position were prepared and the results of cytotoxic activity test showed that the?,?-unsaturated ketone is the active centre and the substitution of the acid moiety at the C-4 position led to significant changes in the cytotoxic activity.The quinone compounds are the main components of Salvia bowleyana,which have better antitumor activity than other components from Salvia bowleyana.