Studies On The Synthesis And Antitumor Activities Of Ananlogues Of Isoquinoline Alkaloids

Today, cancer is harmful to health more and more. It is important way to find out some new antitumor drugs to improve the cure rate. As the natural resources, isoquinoline alkaloids have distinct anticancer activity. They bring a lots of attentions to investigators due to low cost and low side effects.In this study, we tried to elucidate the antiproliferation effects of asimilobine form Magnolia officinalis Rehder on A549 cells and SMMC-7721 cells. To investigate the structure-activity relationships, asimilobine was modified through acetylation and benzoylation reactions. Three derivatives were obtained, including 2-acetylasimilobine, 2,6-diacetylasimilobine and 6-benzoylasililobine. The latter two are unreported compounds. And we also modifiy the berberine through deoxidization and acetylation. Two derivatives were obtained, including tetrahydroberberine and 9-acetylberberine. In vitro modeling of human tumor cells, we use the pharmacological tests to discuss the anticancer activities of 2,6-diacetylasimilobine and 6-benzoylasililobine, and to research antitumor mechanisms of 2,6-diacetylasimilobine by MTT, DNA electrophoresis and cells stained. The results show that the acetylation and benzoylation do not destroy the isoquinoline alkaloids's main structure. The ananlogue 2,6-diacetylasimilobine has more anticancer activity compared with asimilobine. The 6-benzoylasililobine has little anticancer activity compared with asimilobine. The compound 2,6-diacetylasimilobine (80μg/ml) induces cells apoptosis.In one word, the N- property on the B-ring of aporphines has significant effect on the antitumor activity. Above results presents an updated view of the antitumor property of the aporphines and it potential contribution to the development of anticancer agents.