Design, Synthesis And Biological Evaluation Of Emodin Derivatives

Emodin is a typical representative of hydroxy anthraquinone, it has a variety of biological activity, especially the antitumor activity. In order to improve the antitumor activity and selectivity of emodin, I want to utilize the lead compound to synthesize emodin derivatives, which have determinate molecular targets. And the target aims at mitochondria. In this paper several common molecular targets of anti-cancer drugs and corresponding anti-cancer drugs were reviewed. Meanwhile, the mechanism of emodin with DNA and mitochondria was briefly introduced.Our previous studies have shown that the quaternary ammonium salt which is introduced in the 6-position of emodin can improve the activity. But the tertiary amine we used for the synthesis of quaternary ammonium salt before were commercially available, and no tertiary amine containing 9-carbon. Therefore, in order to explore the activity of emodin derivatives containing 9-carbon double long-chain quaternary ammonium salt, the paper designed and synthesized some new tertiary amine containing 9-carbon, and then these tertiary amines were introduced on the flat structure of emodin. In order to expand the flat structure of emodin, some emodin aromatic acylhydrazone derivatives and emodin 1,3,4-oxadiazoles derivatives were also designed and synthesized in this article. In addition, I also designed and synthesized emodin nitrogen mustard derivatives and emodin sulfur mustard derivatives. All the structure of these target compounds were confirmed by 1H-NMR, ESI-MS and melting point measurement. Meanwhile, some of the compounds were also confirmed 13C-NMR and elemental analysis.Cell growth inhibitory effects in vitro of these new compounds were tested by MTT assay. The results show that the antitumor activities of emodin derivatives containing 9-carbon double long-chain quaternary ammonium salt are better than the emodin quaternary ammonium salt derivatives we had reported. The aromatic acylhydrazone and the 1,3,4-oxadiazole introduced on the flat structure of emodin can not improve the antitumor activity. The emodin sulfur mustard derivative has a certain anti-cancer activity. In addition, the compound 34a and the compound 34c were processed by confocal laser experiments. Some of the compounds were also tested by mitochondrial membrane potential experiments, reactive oxygen species experiments and Bcl-2 protein experiments. These results show that the action targets of emodin quaternary ammonium salt derivatives are mainly mitochondria.