Chemical Constituents From Metaplexis Japonica With Reversal Of Tumor Multidrug Resistance

Malignant tumours can cause serious damage to human health life,and its incidence shows a trend of rising every year.Chemotherapy is one of the effective methods for the treatment of malignant tumors,and it is widely used in the process of pre-operation,intra-operation and post-operation.The multidrug resistance is a major obstable to the success of cancer chemotherapy.A new research direction of tumor therapy is to find the tumor mutidrug resistance reversal agent with high efficiency and low toxicity,for the puporse of overcoming the multidrug resistance and recovering the drug sensitivity to the tumor.To investigate the relationship of C₂₁ steroidals with multidrug resistance,we chose Metaplexis japonica,which is rich in C₂₁ steroidal compounds,that belongs to goose down vine plants of Apocynaceae family,as the research object.The effection of crude extract of Metaplexis japonica was evaluated on the reversing activities of doxorubicin（ADM）,cisplatin（DDP）,fluorouracil（5-FU）,and paclitaxel（PAC）toward human drug-resistance gastric carcinoma cell line SGC-7901/VCR,human vincristine-resistance colonic carcinoma cell line HCT-8/VCR,and human paclitaxel-resistance lung cancer cells A549/T.The results indicated that the extracts of Metaplexis japonica has significant effects on sensitization of human drug-resistance colonic carcinoma cell line HCT-8/VCR to doxorubicin（ADM）and fluorouracil（5-FU）,and it also exhibits significant effects on sensitization of human drug-resistance gastric carcinoma cell line SGC-7901/VCR to cisplatin（DDP）,paclitaxel-resistance of lung cancer cells A549/T to cisplatin（DDP）and paclitaxel（PAC）.The chemical constituents were isolated and purified by chromatography on ODS and preparative HPLC.Their structures were elucidated on the basis of chemical and spectroscopic methods,including MS,1D and 2D NMR（1H-NMR,13C-NMR,HSQC,HMBC,H-H COSY and NOESY）spectral techniques.（1）There were 9 compounds are isolated from the stems of Metaplexis japonica by modern isolation and identification of technology.Their identification results: Metajapogenin A（1）,Pergularin（2）,Cybisterone（3）,Pregnane-4-e-3,20-dione（4）,20α-hydroxypregna-4-e-3-one（5）,Pergularin 3-O-β-D-cymaropyranosyl-（1→4）-β-D-oleanodropyranose（6）,2α,3α,19α-trihydroxy-28-norous-12-ene（7）,Lirioresinol B（8）,Pinoresinol（9）.Compound 1 was the new compound and compound 3⁵,7⁹ were isolated for the first time from the plant of Metaplexis japonica.（2）There were 18 compounds are isolated from the shells of Metaplexis japonica by modern isolation and identification of technology.We identificed compounds from the shells of Metaplexis japonica including: Metajapogenin A（1）,Metajapogenin B（2）,Metajapogenin C（3）,Metajapogenin D（4）,Metajapogenin E（5）,Pergularin（6）,Cybisterone（7）,12-O-acetylpergularin（8）,Pergularin 3-O-β-D-oleanodropyranose（9）,Metajapogenin F 3-O-β-D-cymaropyranosy-（1→4）-β-D-digitoxopyranoside（10）,Cyclo-（（S）-pro-（R）-leu）（11）,Dehydrovomifoliol（12）,Threo-anethole glycol（13）,（-）-loliolide（14）,Benzene and ethyl acetate（15）,Aurantiamide（16）,Obtucarbamate A（17）,N,N’-Dimethylformamide-4,4’-methylene dianiline（18）.Their are 6 new compounds,including 1⁵ and 10,compound 7 and 11-18 isolated for the first time from the plant of Metaplexis japonica.We found that the crude extracts of Metaplexis japonica could reverse tumor multidrug resistance and their chemical constituents were isolated and identified.The study benefies will provide theorefical basis for potential development of noval drugs.