Synthesis And Biogical Evaluation Of Novel Derivatives Of Deoxypodophyllotoxin

Podophyllotoxin as well as its derivatives are a kind of natural lignan, which exhibit a pronounced biological activity mainly as antitumor agents and antivirus agents. Some semisynthetic analogues named etopside (VP-16),toniposide (VM-26) and etopophos have already used in chemotherapy for various types of cancer as antitumor drugs in clinical. However, their therapeutic use is often hindered by problems such us poor water solubility,acquired drug-resistance and strong toxicity. In order to find the effective podophyllotoxin compounds with high activities and less toxic against normal cells, two kinds of podophyllotoxin derivatives were designed, synthesized and evaluated for their antitumor activity,as well as their mechanism was discussed in this thesis.1: Based on the excellent anticancer activity of deoxypodophyllotoxin, as well as piperazidine antitumor agents with a better antitumor activity, nine compounds were synthesized. The cytotoxicity against three different cell lines(A549,SiHa,HeLa) were tested. The results revealed that most of these compounds exhibited a stronger cytotoxicity than VP-16 and 4'-demethyl-4- deoxypodophyllotoxin. Cell cycle analysis showed that the derivatives induce G2/M cell cycle arrest and apoptosis in A549 cells.2: Based on the medicine structure modification of L-amino acid, as well as its special psychical effects, twelve compounds were synthesized. The results showed that most of these compounds exhibited a stronger antitumor activity against A549,SiHa,HeLa,HL-60 than VP-16. cell cycle arrested in G2/M cell and apoptosis in A549 cells.