Design, Synthesis Of Imidazole-based Nitronyl Nitroxide Radicals And Reasearchs On Their Antioxidant Activities And Antitumor Activities

Imidazole-base nitronyl nitroxide radicalis are a novel class of bifunctional nitronyl nitroxide radicals containing both nitrogen oxygen dipolar ions and nitroxide radicals. It has the characteristics of easy modification and good water solubility. And it has become one of the research hotspots in many scientific research fields nowadays. This thesis focus on design and synthesis of eighteen novel imidazole-based nitronyl nitroxide radicals, and research on their antioxidant activities and antitumor activities. Details are as follows.1. Eighteen novel imidazole-based nitronyl nitroxide radicals 4a⁴r were designed and synthesized. The synthetic methods of the crucial intermediate 2,3-dimethyl-2,3-di?hydroxyamino?butane were improved. The structures of all intermediates and final products were analyzed by 1H NMR?13C NMR?HRMS?EPR spectra.2. Research on the elimination function of 4a⁴h to DPPH were carried out. The results showed that eight novel imidazole nitronyl nitroxide radicals showed scavenging effect on DPPH. In a certain concentration range?0.01 ?mol/m L-2.40 ?mol/m L?, the scavenging effect of them increased with the increase of concentration. Among them, 4a exhibited more active antioxidant activity compared with Tempol, while 4b had the same effect. They all have the potential value of further research and development.3. Research on the protective effect of 4a, 4b, 4f and 4i on H₂O₂-induced oxidative damage in Hela cells, Hep G2 cells and HK-2 cells were also implemented. The results showed that these novel imidazole-based nitronyl nitroxide radicals can protect the cells which containing Hela cells, Hep G2 cells and HK-2 cells from H₂O₂-induced oxidative cytotoxicity.4. Preliminary research on the antitumor activities of 4a, 4b, 4f and 4i on Hela cells and Hep G2 cells were also implemented. The results showed that 4a and 4i had better antitumor activities on Hela cells and Hep G2 cells.