Design,Synthesis And Activity Analysis Of Emodin Lipophilic Cationic Compounds

The design and synthesis of the anti-cancer drug is one of the most important research contents for medicinal chemists. The pattern of the research and development for the anti-cancer drug is to determine a basic skeleton as a lead based on the bonding mechanism between the drug molecules and targets, and then introduce the necessary pharmacophore to achieve a good therapeutic effect. Synthesizing the new antitumor drugs and looking for the targets of drug acts are the important direction of tumor therapy research. DNA and mitochondria, These two targets of drug action and some simple mechanism of antitumor are introduced in this paper, after understanding the mechanism between pharmacophore and target, we introduced the corresponding pharmacophore into the lead and complete the design and synthsis of the anti-cancer drug.Emodin(1,3,8-trihydroxy-6-methylan-thraquinone) is one of anthraquinone analogues with a flat structure, it can inhibit various tumor cells. As to its lower inhibitory,we choose the emodin as the lead and make the necessary modification. From the researching on emodin in recent years, the reserchers found out that people will gradually choose the mitochondria as targets of drug action. So we choose the mitochondria as the target and have synthetized some lipophilic cationic compounds and studied their inhibition on tumour cells by changing the kinds of heteroatom, the number of the cations and the length of carbon chain.These compounds have been characterized by 1H NMR、13C NMR、mass spectrum、element analysis and melting point of compounds.The inhibition activities to leukemia cell line HL60、lymphoma Molt4、Colon26 and embryonic lung fibroblasts HELF cells of these compounds have been tested by MTT. From the result of the test we can conclude that the anti-cancer activities of lipophilic cationic compounds are much better than the emodin itself, and the lipophilic cationic compounds containing heteroatom P are more effective than those containing heteroatoms N for the inhibition of tumor cells, especially the emodin derivatives containing triphenylphosphine groups.