Design,Synthesis And Activity Study Of Antitumoral Drug

Malignant tumor has been endangering people's health. According to statistic of WHO, the number of people, who were dead because of malignant tumor, reaches 69 million in 5 billion people of the world every year, even is increasing year after year. So every country is attaching importance to tumor studying and anti-tumor drugs at all times, and anti-tumor drugs have taken out great progress. In order to design pharmic value of compounds, we select different metal atoms and several kinds of organic ligand to synthesize some compounds in the dissertation, characterized by element analysis, IR, 51V NMR and X-ray. The biological effects were systematically investigated. Also anti-tumor mechanism was studied by flow cytometry. The main results indicated:1. Na₄Co(H₂O)₆V₁₀O₂₈·18H₂O (CoV₁₀) is synthesized, and characterized by IR spectra and X-ray. CoV₁₀ show higher antitumor activity in vitro and in vivo. Acute toxicity test results show that CoV₁₀, whose LD50 is 60.93 mg·kg^-1 is a medium toxic material. In addition, using flow cytometry analysis, CoV₁₀ has brought change of cell cycle and cell apoptotic. The investigation on the interaction of CoV₁₀ with DNA suggests that CoV₁₀ may have ability to specifically action with DNA.2. Cyclopentanedione vanadium-oxygen compound (CPD-VO) is synthesized, and characterized. Absorption peaks of V=O and characteristic peaks of correlation group can be seen in IR spectrum. The singlet is seen in 51V NMR. The valence of vanadium is determined. CPD-VO show higher antitumor activity in vitro and in vivo. Acute toxicity test results show that CPD-VO, whose LD50 is 179.92 mg·kg^-1 is a medium toxic material. In addition, using flow cytometry analysis, CPD-VO has brought change of cell cycle and cell apoptotic. The investigation on the interaction of CPD-VO with DNA suggests that CPD-VO may have ability to specifically action with DNA.3.β-diketone complexes are synthesized, and characterized by IR spectra and X-ray. Complexes show lower antitumor activity in vitro.