| At present, cancer has become the second killer of the human, next to the cardiovascular and cerebrovascular diseases, threating to human life seriously. The problems caused by cancer have increasingly become a heavy burden on the social and economic development. According to the World Health Organization, about8,000,000people are killed by cancer every year. Therefore, the prevention and treatment of cancer is a very difficult task. As the limited knowledge of cancer lesions and metastasis, as well as the mechanism of anti-cancer drugs to cancer cells mankind still can’t completely cure cancer, at best, only extend survival time of cancer patients restricted. The characteristics of cancer, which including the long-term existence, the substantial increasing in new cancer cases and the difficulty to cure, determine the increasingly demand for anti-cancer drugs of human society.After more than half a century’s effort, tremendous progresses were made in chemotherapy ways to treat cancer, and many significant achievement in many areas. For example, the treatment of testicular cancer with cisplatin, the partial or complete remission rate is up to85%, the5-year survival rate is higher than90%. Another example is Hodgkin’s disease, with the natural remission rate below5%, but after the chemotherapy, the complete remission rate reached over80%. However, many other types of cancer are difficult to be successfully treated by chemotherapy or other methods. The most popular cancer, lung cancer, has the5-year survival rate below15%. More seriously, the5-year survival rates of liver and pancreatic cancer after chemotherapy only reach10%.Furthermore, with respect to the traditional anticancer drugs, two major bottlenecks, the significant side effects to human body and multidrug resistance, still restrict their development and application. The development of new anticancer drugs become the most pressing needs in the field of drug development, as well as one of the most serious challenges.During a long-term construction of the combinatorial library of Thiazolidinones and biological activity screening, our laboratory developed a series of lead compounds with good anti-cancer activity. Among various characteristics, two performances are outstanding:1. The selective cytotoxity to cancer cells, but innocent to normal cells;2. In the treatment of lung cancer, this kind of compounds have good inhibit activity to H460RT cell line, suggesting these compounds are potential candidates of Taxol to treat lung cancer. To further investigate these excellent features, our lab started many project on molecular structure level. We focused the entre point on the Michael Acceptor in the Thiazolidinones molecule, and established two synthetic route to synthesis the Thiazolidinones molecule without Michael Acceptor(one route is for restructure the active lead compound, and the other is for the follow-up combinatorial synthesis by diversity amino reaction), paving the way for finally demonstrating the anticancer mechanism of Thiazolidinones. Simultaneously, we have introduced the diversity amino reaction into the former synthetic route successfully, extending the diversity of the former combinatorial library, and laying a good foundation for screening the new active compounds.Experimental innovation:1. We established a new synthetic route to realize the synthesis of novel Thiazolidinones without Michael Acceptor;2. We introduced the diverse amino reaction into the synthetic route to enrich the diversity of the combinatorial library;3. We enhance the solubility of Thiazolidinones significantly by this project;4. We set the stage for further investigating the effect of Michael Acceptor to the anticancer activity of Thiazolidinones and searching the drug target of Thiazolidinones. |
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