Preliminary Studies On Selective Synthesis Of Mercaptopurine-Ribonucleoside And Mercaptopurine-Ribonucleoside-Bonded Porphyrins

The non-communicable diseases, such as malignant tumor (cancer), cardiovascular disease, and diabetes are becoming the most deadly "killer" for human. Cancer was the biggest threat among them. Leukemia is a serious body immune system cancer. At present, chemotherapy is widely applied for clinical leukemia treatment. Antineoplastic antibiotic drug is one of the effective treatments for leukemia. However, antineoplastic antibiotic drugs used by now mostly have the disadvantage that they can not be directionally transported to the cancer cells and they have strong poison and side effect for human. Therefore, it is very important to explore and develop new anticancer drugs which are more active and specific in killing the cancer cell. In this thesis, according to the theories and methods of designing analg drugs and combination principles, theβ-mercaptopurine ribonucleoside-porphyrins were designed and studied. In despite of improving and discussing the experiment conditions, they were not obtained. We analysed and discussed the results, characterized the compounds we obtained. The results were testified by a series of experiments and their anticancer biological activities were preliminarily studied. The main contents were summarized as following:(1) Recent research in application of porphyrin was reviewed. The synthesis and applicationsin of nucleoside-porphyrin and purine nucleoside were summarized here.(2) 9-β-D-mercaptopurine nucleoside were designed and synthesized selectively and their optimal conditions were obtained from the orthogonal experiments.(3) The excellent synthetic condition, simple sepration method of 5-(4-bromoethoxy)phenyl-10,15,20-triphenylporphyrin were obtained.(4) According to the theories and methods of drug design (analog design and combination principles), three kinds ofβ-mercaptopurine ribonucleoside-porphyrins were designed and studied. We failed to get the target molecule but a new compound whose structure was characterized by MS, IR, and1H NMR spectra. The unexpected results were analysed and discussed and testified by a series of experiments.(5) The ultraviolet-visible absorption spectra and fluorescence spectra were measured for above compounds. Investigation of their biological activities with two kinds of tumor cells including cell cycle(HELA) and liver cancer(BEL-7402) were preliminarily cultivated for the new porphyrins using MTT method. The result showed that these compounds can inhibit these cancer cells in some way.