Synthesis Of Antimony Analogs Based On Natural Nitrogen Sources And Their Antitumor Activities

The natural alkaloid is a kind of important nitrogen-containing compounds,and the monoterpenoid indole alkaloids are widely concerned by medical researchers due to its excellent and extensive biological activities.The skeletons of natural products are complex and novel,but their low content and simplex substituent groups reduce the efficiency of lead compound discovery.Therefore,we proposed the synthesis of a variety of monoterpene indole alkaloid-like analogues with genipin by biomimetic synthesis method,and then carried out the systematic antitumor activity screening.The structural types,the basic principles and methods about biosynthesis and chemical synthesis of monoterpene indole alkaloids were reviewed.Then,the principles,advantages and disadvantages of the methods about cell activity test,such as staining,clone formation,instrumental analysis and colorimetry,were briefly introduced.Based on the idea of biogenic synthesis and combinatorial chemistry via the biomimetic reactions of iridoid genipin and natural nitrogen-containing compounds,our previous research about syntheses about monoterpene indole alkaloids-like and the antitumor activities were carried,the results showed that the antitumor activity of the compound T4 was obvious,the IC50 value was 0.90 μM.A further research of monoterpenoid indole alkaloid-like analogs was continued as following: 5 genipin derivatives and 33 target compounds were prepared(M2a,M4,M5,M6 and M8),including 14 single indole alkaloids,10 bisindole alkaloids,6amino acid alkaloids and 3 pyrimidine alkaloids.The activity of some monoterpenoid indole alkaloid-like analogs against 5 tumor cell lines(leukemia cell line HL-60,hepatocellular carcinoma cell line SMMC-7721,lung cancer cell line A-549,human breast cancer cell line MCF-7,human colon cancer cell line SW480)was tested.The results showed that 6 compounds showed good inhibitory activity,the inhibitory activities of compound 15(IC50 value was 0.70 μM)in vitro against 5 kinds of tumor cells were higher than the positive control cisplatin(DDP;IC50 value was 3.50 μM),but weaken than that of paclitaxel(Taxol).The inhibitory activity of compounds 17,19,and 21 on leukemia cell line HL-60 was similar to that of positive control DDP.The inhibitory activity of compounds 22 and 24 on HL-60 was slightly lower than DDP.Finally,the chemical work and activity screening results of monoterpenoid indole alkaloid-like analogs were discussed,structure-activity relationship was preliminary studied,which provided a scientific basis for the further study.