Design,Synthesis And Anticancer Activities Of Lipiophilic Cations Of Anthraquinone

Mitochondria are the only organelles executing cell apoptosis.Compared with normal cells,Cancer cells own special structure and function in mitochondrial,as below:(1)The mitochondrial membrane potential was significantly higher;(2)Intolerant to the oxidative stress of ROS;(3)Mitochondrial functions are easily damaged,and cancer cells tend to supply energy by glycolysis.Traditional lipophilic cations mainly advantage of the first feature.Anthraquinone lipophilic cation comprehensive utilize of the first two characteristics,it is expected to become a new anticancer drug.A series of anthraquinone lipophilic cations were synthesized and studied anticancer activity in this paper.As follows:a-naphthoquinone methane quaternary ammonium salt,aloe emodin quaternary ammonium salt and reduced product anthrone quaternary ammonium salt,sulfonium salt of emodin and emodin sulfide was synthesised and evaluated antitumor activity.The results showed that Quinone structure of which transferring electron and the positive charge is important for the anticancer activity.1,4-dihydroxy anthraquinone as primer,various of hydroxyl anthraquinone quaternary ammonium salts was synthesised.The results showed that simple increasing of Pharmacophore could not significantly improve the anticancer activity.Changing one of them to water soluble,but activity cutted down,showed that the water soluble have adverse effects on anticancer activity.Aloe emodin Quaternary ammonium salt iodine ester prodrug was designed and synthesized.The hydrolysates can damage the energy pathway and inhibit glycolysis of the cancer cells.Comprehensive utilization of multiple features during one molecular would be a good design idea for anticancer drug.Synthesis of the hydroxy anthraquinone and emodin thiourea both showed good activity,indicate quinoid structure combined with thiourea group can produce good anticancer activity.Also synthesized anthraquinone thiourea quaternary ammonium(phosphonium)salt,and showed good activity.The principle of anthraquinone thiourea with good antitumor activity remains to be further studied.