Synthesis And Antitumor Activity Of Multi-Substituted Isatin Derivatives

Isatin, named indole dione or 2,3-indole quinones, is an endogenous substances existing in mammalian tissues, body fluids and traditional Chinese medicine Indigo. Literature surveys reveal that various derivatives of isatin possess diverse activities such as anticancer, antibacterial, antiviral and antituberculosis and other activities. In recent years, the biological and pharmacological properties of isatin and its derivatives have attracted extensive attention from academic and industry. Many types of chemical reactions can occured on the pyrrole ring and benzene of isatin and generate derivatives.In the past, many research have been focused on the synthesis of mono-substituted isatin derivatives on the benzene ring and pyrrole ring and lack of the systematically study on the synthesis and biological activity of multi-substituted isatin on the benzene ring. This thesis describes synthesis and antitumor activity of 4,5,6,7- and 1,3,7-substituted isatin derivatives.From differently substituted anilines, four different synthetic routes were design through Sandmeyer method (oxime, Friedel-Crafts reaction), bromination, nitration, oxidation, esterification, diazotization reduction and alkylation to provide 68 target compounds, which were characterized by 1H NMR,13C NMR and MS. Among them 41 compounds have not been reported.The in vitro anticancer activities of the target compounds were evaluated against three cancer cells (human leukemia cell K562, human hepatoma cell HepG2 and human colon cancer cell HT-29). The results suggested that the multi-substituted isatin derivatives possesses the electron withdrawing nitro group at 5-position, the weaker electron-withdrawing halogens at 4-and 6-positions, the carboxylate or carboxylic acid amide at 7-position, the benzyl at 1-position and the 3-carbonyl unchanged are favorite to the anti-tumor activity. This study of multi-substituted isatin derivatives will be helpful to the further investigation of noval isatin-based antitumor drugs.