Abstract:

A series of 2-[1-(2-formylamido-3-phenylpropionyloxy)alkyl]-1,4-dihydroxy-9,10-anthraquinone(2-FPADHAQ) derivatives was designed and synthesized. Their antitumor activities were tested against L1210 tumor cells and P388 mouse leukemic tumor cells in vitro and in ICR mice bearing sarcoma 180 cells in vivo. Overall, the introduction of 2-formylamido-3-phenyl-propanoic acid(2-FPPA) into the C-2-alkyl side chain C′-1 hydroxy group in 2-(1-hydroxyalkyl)-1,4-dihydroxy-9,10-anthraquinones(2-HDHAQ) enhanced the antitumor activity compared with the starting materials. 2-FPADHAQ with alkyl chains longer than the pentyl group had negligible activity, whereas compounds 2b, 2c, 2d and 2epossessing shorter chains demonstrated moderate cytotoxic activity[50% effective dose(ED₅₀) of L1210 and P388 are 2.61-4.75 and 5.84-8.74 μg/mL], whereas compound 2l with an aromatic system showed strong cytotoxic activity. T/C(%) values[(average survival days in the test group)/(average survival days in the control group)×100%] also show that the introduction of 2-FPPA into the side chain of 2-HDHAQ enhanced antitumor activity. These data suggest that the introduction of an amino acid into the starting material may increase its affinity for DNA or its selectivity for proliferating cancer cells.

Key words: Anthraquinone, Antitumor, Cytotoxicity, Phenylalanine