Design,Synthesis And Biological Evaluation Of Water-soluble Emodin Derivatives

Emodin,which is a kind of anthraquinone derivatives,having a series of good biological activities,such as anti-inflammatory,antibacterial,antitumor,and so on.The coplanar structure makes it easy to intercalates into base pairs of the duplex DNA because of its coplanar structure with three rings.In a result,affecting the proliferation and transcription process of DNA to reach the purpose to kill the tumor cells.the carbonyl oxygen of anthraquinone can produce reactive oxygen species(ROS)in cancer cells,named the free radicals,the tumor cells will collapse and apoptosis under the affection of ROS when the intracellular stress of ROS reaches a certain extreme value.In my research subject,I synthesized a total of 13 kinds of quaternary ammonium salts derivatives as the forerunner of emodin for further improving the water soluble and cell cytotoxicity of emodin based on the two kinds of anticancer mechanisms.Our previous studies found that the antitumor activity of emodin with quaternary ammonium salt was improved greatly than that of this kind of natural compound.The cytotoxicity of emodin quaternary ammonium salt derivatives with short carbon chains is low,interestingly,the cytotoxicity of those derivatives with two long carbon chains is obvious higher,because the lipophilic properties are very strong of this kind of emodin quaternary ammonium salt derivatives with two long carbon chains,while the water soluble of them are very poor,In order to further improve the anticancer activities and water soluble,I designed and synthesized five emodin bis-quaternary ammonium salts derivatives,In my experiments,I got the intermediate product which was named emodin tertiary amine by using the phase transfer catalyst(TEBA),Then,I got the target product by the reaction between the emodin tertiary amine and quaternary ammonium salts with iodine atom,For getting pure target products,the method was used by column chromatography with gradient elution to remove almost impurities.On the other hand,I designed and synthesized multiple emodin quaternary ammonium salts derivatives containing hydrophilic groups(like the ethers and glycol groups),The water soluble of those emodin quaternary ammonium salts derivatives were improved greatly,the antitumor activity also had improved correspondingly,The structure of all of these new compounds were characterized by 1H NMR,ESI-MS HRMS,and melting point,part of them also characterized by 13C NMR and Elemental analysis.The great majority of these new compounds have been tested in cell growth inhibitory of effects in vitro by MTT assay.The result demonstrated that the antitumor activity of emodin bis-quaternary ammonium salts derivatives is better than that of emodin quarterly ammonium salt derivatives.In another way,the water-soluble of emodin bis-quaternary ammonium salts derivatives also have improved greatly than before,alkylation ability of them is enhanced with two positive charge,benefited to the insert function between emodin and DNA,Though the water soluble with water soluble groups of emodin quaternary ammonium salts is greatly improved,the antitumor activity is reduced,this consequence indicates the fat-soluble of emodin quaternary ammonium salt makes contribution to drug molecules through the cell's membrane enhancing cytotoxicity,but the result is limited to activity test in vitro.