Synthesis And Properties Of Anthraquinone Targeted Anti-tumor Compounds

1,4-Disubstituted anthraquinones demonstrate potent anti-tumor activity and have beenused widely in clinic since 1980s. Their clinical use is limited by tumor resistance and toxicitytowards healthy tissues. On the basis of the anthraquinones antitumor drugs, connected themto the targeted groups can be more targeted anti-cancer effect. This paper is built on thebasis of the anticancer effects of anthraquinones. Connected targeting molecules-biotin withthem to produce biotin-mediated 1,4-disubstituted anthraquinone and 6,9-disubstitutedaza anthraquinone compounds.The reaction of phthalic anhydride with hydroquinone resulted in the importantintermediate 1,4-[(2-aminoethyl)amino]-9,10-anthracene dione(Ⅱe) by using four differentmethods. The fourth method is the best response line. The compound ofⅡe was reacted withbiotin to make biotin-mediated 1,4-[(2-aminoethyl) amino]-9,10-anthracene dione(Ⅱf). Therelated compounds were characterized by TLC, IR and1H-NMR. Improved intermediatecompound 1,4-dihydroxyanthraquinone separation and purification methods, the first attemptto use ethyl acetate and recrystallization of the crude product. The product was purified by atransolid orange granualar cryatals. The appropriate reaction conditions ofⅡe : the bestmaterials ratio is 1:20, reaction temperature is 50℃, reaction time is 1h, reaction solvent isdioxane: water = 1:1.Pyridine-3,4-dicarboxylic acid was synthesized by oxidizing isoguinoline with sulfuricacid and fuming nitric acid. After its intramolecular dehydration by acetic anhyddide, thepyridine-3,4-dicarboxylic is formed. Using four different methods to produce the importantintermediate 6,9-bis-[(aminoethyl) amino]benzo isoquinoline-5,10-diones (Ⅲe). The secondmethord is on the yield of 90.46%. And then connected to biotin with DCC to producebiotin-mediated 6,9-bis-[(aminoethyl) amino]benzo isoquinoline-5,10-diones (Ⅲf).Anti-tumor in vitro activity of target compounds IIe, IIf, IIIg and III h aginst L929 cells,A549 cells and Hela cells were studied in this paper. The resules show that the compoundis minimal toxicity to normal cells L929. But they showed good growth inhibition ontumor cell A549 and Hela. The IC50:Ⅲe >Ⅲf>Ⅱe >Ⅱf. The compoundⅢe showed thebest antitumor activity. The IC50:Ⅲe >Ⅱe, indeed N improve its ability to inhibit growth oftumor cells. For the normal cells, The IC50:Ⅱe >Ⅱf，Ⅲe >Ⅲf，indeed the biotin targetingrole can reduce the toxicity of compoundⅡe andⅢe on the non-tumor cells L929.