Study On The Design, Synthesis And Antitumor Activity Of Imidazole Salts Of 2 - Substituted Indoline And Spiro Oxidation Indole

Cancer, as a disease with high morbidity and mortality rate is seriously harmful to people’s health. Therefore, the development of drugs with good antitumor activity is one of the focus areas of medicinal chemistry. So far, the chemists have isolated natural products from natural drugs and found many pharmacologically active natural products. Some of them are indole and imidazole derivative with excellent antitumor activity. In this thesis, two types of indole-imidazolium salt were synthesized and all synthetic compounds were evaluated against antitumor cytotoxic activity, in order to find high selectivity and efficiency novel anti-tumor lead compounds.This thesis consists of three chapters.In Chapter1, the bioactivity of the spirooxindole, indoline and imidazole derivatives was briefly reviewed.In Chapter2, four series, a total of25new indoline-imidazolium salts were synthesized. From the in vitro antitumor activity screening, most of these imidazolium salt compounds showed high cytotoxic activity and had obvious selectivity on leukemia cells (HL-60), such as compound b21, b25, b26, b28and b32. Interestingly, compound b25, bearing a naphthylacyl substituent at position-3of2-methyl-benzimidazole, was found to be the most potent derivative with IC50values of0.24-1.18μM against all of the human tumor cell lines investigated and more active than DDP.In Chapter3, starting material were isatin and cinnamic acid. The isatin’s nitrogen was protected by methyl protection and cinnamic acid was transformed into cinnamic aldehyde. Then both of them stir with proline through the1,3-dipolar cycloaddition reaction with one pot method to synthesis spirooxindole. Finally, by activation of hydroxy group and hybridization with imidazole and bromine, the22new spirooxindole-imidazolium salts synthetized. The structures of all compounds were confirmed by’H-NMR,13C-NMR, HR-MS, IR and X-ray. The research on antitumor and antibacterial activities is in progress.In this thesis, a total of47new indole-imidazolium-salts compounds were synthesized, and most of them showed excellent anti-tumor activity. Furthermore, on the basis of this thesis, optimizing the structure of indole-imidazolium salts were expected by further structure-activity analysis in order to find lead compounds with biological activity.