Design, Synthesis And Activity Evaluation Of Tilorone Analogues As Potential Anticancer Agents

Tilorone is the first synthetic, small molecular weight interferon inducer with anticancer and antiviral activities. This thesis focuses on synthesis and activity evaluation of its analogues.In chapter one, the anticancer agents were classified by their action mechanism. Their functional groups were detailed introduction. Some representatives of each kind of drugs were listed with their indication. The side effects of these drugs were also mentioned.In chapter two, the action mechanism of tilorone was elucidated. The pharmacophores of this class of compounds were summarized as well as the pattern of ligand-receptor interaction. Based on previous research, the design proposal of this thesis was put forward.In chapter three, two series of tilorone analogues were synthesized in good yield. The thirty-eight compounds were characterized by1H NMR,13C NMR, elemental analysis and mass spectra. The data are shown in this part.In chapter four, the in vitro anticancer activities of synthesized compounds were evaluated by MTT assay. The compounds with high activities were then performed cytotoxic assay. There are ten new compounds out of38compounds which are more active against cancer cells.2c and5d are the most potent compounds in both anticancer activities and selectivities. The structure-activity relationships were outlined at the end of this part.In chapter five, the active compounds were carried out pharmacophore modeling in MOE. The compounds2c,5d and tilorone were also processed docking experiments towards DNA G-quadruplex for understanding of possible ligand-receptor interaction pattern.