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The substituted anthraquinones as bioreductive drugs have been widely developed and become one of the most hotspot in the field of the anticancer research since Italy scientist Dimarco Arcamone and Bonadonna studied and approved the curative effect of Daunorubicin and Adriamycin in 60s last century.At present,there are many breeds of anthraquinones anti-tumour drugs that were applied in clinic,such as Mitoxantrone and Daunorubicin.In this paper,a series of amino substituted anthraquinones were designed and synthesized on the basis of bioreductive drugs acting mechanism.The compounds 1,4-bis（2-aminoethylamino）-5,8-dihydroxyanthracene-9,10-dione（1）,1, 4-dihydroxy-5,8-bis（2-hydroxyethylamino）anthracene-9,10-dione（3）,1,4-bis（2-aminoethy lamino）anthracene-9,10-dione（4）and 1,4-bis（2-hydroxyethylamino） anthracene-9,10-dione（5） were synthesized by the condensation,oxidation reaction of hydroxy-2,3-dihydroanthracene -9,10-dione with ethane-1,2-diamine and acetamide.The reaction conditions,such as the reaction temperature,the materiel ratio and so on were optimized,separation technology was improved,too.All those compounds were characterized by IR and 1H-NMR.Results showed that 5,8-hydroxy with 9,10-carbonyl could form intermolecular hydrogen-bond which could influence the melting point and yield of compounds.The compounds N,N′-（2,2′-（5,8-dihydroxy-9,10-dioxo-9,10-dihydroanthracene-1,4-diy 1）bis（azanediyl）bis（ethane-2,1-diyl））dinicotinamide,N,N′-（2,2′-（5,8-dihydroxy-9,10-dioxo-9, 10-dihydroanthracene-1,4-diyl）bis（azanediyl）bis（ethane-2,1-diyl）） diisonicotinamide,N,N′-（2,2′-（9,10-dioxo-9,10-dihydroanthracene-1,4-diyl）bis（azanediyl） his（ethane-2,1-diyl）） dinic otinamide,N,N′-（2,2′-（9,10-dioxo-9,10-dihydroanthracene-1,4-diyl）bis（azanediyl） bis（ethane -2,1-diyl））diisonicotinamide were synthesized by the acylation reaction of compounds 1 and 4 with nicotinoyl chloride and isonicotinoyl chloride.The reaction conditions and separation technology were optimized.All those compounds were characterized by IR and 1H-NMR.The results showed that the different locations of the hydroxide and N-heterocyclic result in the differences of reaction degree,reaction conditions and product charactristics.Anti-tumour in vitro activity of the synthesized compounds aginst A549 cells,EC9706 cells and LoVo cells were studied in this paper.The results show that the compound 4 has evident activity and the dosage-effect relation,the IC50 are 10.78μmol·mL-1,16.13μmol·mL-1, 6.29μmol·mL-1.The compounds 3,6,7 have a little activity,but they are more active when concentration are upto a certain degree.Structure-activity analysis showed that:Hydroxide of anthraquinone ring has an important influence of diffusion and permeability on the histiocyte cells.Hydroxide in the end position of amino chain could reduce the affinity and the antitumor activity of the compounds. The length of carbon chain and the location of N-terminal could affect the "N-O-O" triangular ring structure,and change its capacity to suppression of DNA replication.Extending the length of carbon chain could increase hydroxide antitumor activity.N-heterocyclic compounds could improve the structure-activity relationship and the ability to insert DNA molecule to prevent the replication of DNA.
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