Synthesis And Antitumor Activity Of Indole-3-glyoxylamide-4-podophyllotoxin Derivatives

Podophyllotoxin, as an excellent anti-tumour plant compound, plays an important role in medicine research. Synthesis and activation study of its analogs become a hotspot in anticancer study. Over the years, our group has been involved in the chemical transformation of podophyllotoxin and has prepared a large number of podophyllotoxin derivants with super anticancer activity. Among them,(substitutedindol-3-glyoxylamide)-4-podophyllotoxins represented. They were designed using association strategy based on indibulin’s planar indole-3-glyoxyl structure and podophyllotoxin. However, they have bad stability. In order to improve their stability, the new substituted indole-3-glyoxylamide-4-podophyllotoxins were designed by changing the substitution of indole ring.274β-(substitutedindol-3-glyoxylamide)-4-podophyllotoxins and54β-(substitutedind--ol-3-formylamide)-4-podophyllotoxins were synthesized and their chemical structures were identified by1H-NMR、HR-ESI-MS as well as melting point, and they all have not been reported in literature. They were tested cytotoxicity in vitro by the standard MTT assay against HeLa cell lines. The result showed that the cytotoxicity of14analogues was comparable to that of VP-16. The structure-activity relationship of the two series compounds were investigated according to the in vitro pharmacological results, which laid the foundation for further research.