| Podophyllotoxin, an important lignan compound which extracts from natural. The Podophyllotoxin and its derivatives have a variety of biological activity, including anti-tumor, anti-virus, anti-rheumatic activity and so on. At present, the most common uses the compounds of Podophyllum is as the basis compounds of antineoplastic agents and anticancer drugs. Now, the clinical podophylin anticancer drugs etoposide and others are still widely used. However, their therapeutic use is often hindered by problems such us poor water solubility、acquired drug-resistance and strong toxicity. Triazole compounds are developed with the theory of "click reaction". Triazole compounds are found structural rigidity, stability and electron-rich nature in Drug Research, the structure of the triazole can be used as main pharmacophore activity alone, while also can be used as amide bond in the electronic emission so that can change some properties of the parent compound.Considering4-N-replaced derivatives of Podophyllotoxin have the excellent anti-tumor activity, and to improve water-soluble and so on. This thesis made a combination of podophyllum and triazole structure. A series of4β-(1,2,3-ttriazole)-podophyllum derivatives were designed and synthesized, and their antitumor activity were tested in vitro. The specific process is use podophyllotoxin as the parent compound, then use of "click chemistry" reaction to the introduction of the triazole structure in4-position. Then use the intermediate compounds esterification with different amines, get a series of final products. The use of human lung cancer cells (A-549), gastric carcinoma cells (BGC-823) as a screening cells, use of VP-16, DDPT as control, test the products’antitumor activity in vitro. After the trial we found that a number of compounds can significantly inhibit the proliferation of tumor cells. Morpholine ring modified compounds, the IC50value for A-549\BGC-823cells is8.1E-07mM and4.3E-06mM. |
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