Synthesis Of The Compounds Of Metalloporphyrin And Chlorins-5-Fluorouracil

Porphyrin, metalloporphyrin and chlorins have special affinity with cancer cells because of their distinctive structures. If taken up, they can be absorbed by tumor tissues selectively. With the existence of oxygen, these photosensitizers activated by light of specific wavelength yields the singlet-state oxygen which kills cancer cells directly.5-Fluorouracil (5-Fu), which has the similar structure with uracil essential to the cancer cell, is a sort of prevailing antimetabolic drug used in clinic. It contests with uracil in the same enzyme system, blocks the metabolic linkage, impedes the synthesis of DNA and prohibits the propagation of cancer cells. As a kind of antitumor drug, 5-fluorouracil has effect on restraining many sorts of cancer cells, but it also does harm to normal cells seriously while putting tumor cells to death.Chlorins, the second generation photosensitizer, are superior to porphyrins in the following aspects: enhanced absorption in far infrared region, strengthened molar extinction coefficient, increased therapy depth, less dosage, shorter retaining time and smaller toxic effects. Meso-tetra(3-hydroxyphenyl)chlorin(m-THPC), an example of the second generation photosensitizer, has attained delightful outcomes in the photodynamic therapy to many species of cancer cells. At the present time, its study has access to clinical phase. According to the principle: bioisostere, 5-(3-hydroxyphenyl)-10,15,20-tri(3-chlorophenyl) chlorin was selected to take place of m-THPC in our group. As a result, a series of m-chlorophenyl chlorin-5-fluorouracil compounds with various length of carbon chain were synthesized.Porphyrin, metalloporphyrin and chlorin were used as carrier to modify 5-fluorouracil with the expectation that they could bring 5-fluorouracil to tumor tissues directly in order to abate harms to normal cells and toxicity of 5- fluorouracil. In recent years, there is a tendency that scientists combine photosensitizers with anticancer drugs to synthesize compounds which had dual functions mentioned above.In the thesis, we synthesized and characterized two new m-chlorophenyl porphyrin-5-fluorouracil compounds, six novel manganese (â…¢) porphyrin-5- fluorouracil complexes and six novel m-chlorophenyl chlorin-5-fluorouracil compounds. The results were as follows:1. Six novel manganese(â…¢) porphyrin-5-fluorouracil complexes have been characterized by UV-Vis, IR and MS spectra.2. Two new m-chlorophenyl porphyrin-5-fluorouracil compounds and six novel m-chlorophenyl chlorin-5-fluorouracil compounds have been characterized by UV-Vis, IR, 1HNMR and MS spectra.3. Ex and Em fluorescence spetra of six manganese (â…¢) porphyrin-5-fluorouracil complexes and six m-chlorophenyl chlorin-5-fluorouracil compounds were investigat- ed. Our study indicated that the fluorescence intensity of chlorins was stronger than that of manganese (â…¢) porphyrin.