Studies On The Synthesis And Properties Of Amide Linkage Cytidine-bonded Porphyrin

Cancer is one of the serious diseases which affect human beings′health. However, it is a common problem that current clinical use of drugs on cancer cells and on normal cells is identical because they can not efficiently concentrate in tumor tissue. Therefore, it is an important issue in medicine and pharmacology to synthesize some new compounds as anticancer drugs that can concentrate to higher concentrations in malignant tumors than in normal tissus in order to improve drug bioavailability and reduce side effects. In this thesis, according to the prodrug principle and using the porphyrin can accumulate in cancer cell rather than surrounding normal cell, cytidine-donded porphyrins were designed and synthesized via an amide bond, and then preliminary studies on their anticancer activity and interaction with BSA, DNA.The main contents were summarized as following:(1) According to the literature, the mechanism of porphyrins′direction in cancer cells and the application progress of porphyrin and cytidine and cytidine-donded porphyrins in anticancer researches were reviewed. And also introduces the strategy of the structure modification for cytidine.(2) Analogues design and Flatten principle are two important ways which are based on principles of drug design. According to the prodrug principle and using the characteristics of the molecular structure of porphyrin and cytidine, cytidine-donded porphyrins were designed and synthesized via an amide bond, and were charactered by 1H NMR, UV, IR, and MS.(3) The interaction of cytidine-donded porphyrins with BSA was investigated by fluorescence spectrum under physiological conditions.The experimental results show that cytidine-donded porphyrins have a strong combination of constant with BSA and that is a static quenching process.(4) Their anti-tumor activities against cell line Bel-7402, Hela, MCF-7 and LO2 were tested by MTT method intro, with Tegafur positive control. The in vitro anticancer activity test showed that the synthesized compounds are the potential anticancer agent and the substitutends with F at the C-5 position of the cytidine ring have a very important effects on anticancer actives.(5) The interaction of cytidine-donded porphyrins with ctDNA was investigated by UV spectrum and fluorescence spectrum. The results showed that ionic strength, anionic quenchers KI and other have certain impact on the interaction between cytidine-bonded prophyrins and DNA. There are two modes of action which are groove and static and the substitutends at the C-5 position of the cytidine ring have a very important effect on binding ability between cytidine-bonded prophyrins and DNA.