Synthesis and evaluation of the antitumor activity of 4,5-diamino-substituted 1,2-benzoquinones.
A series of 4,5-diamino-substituted-1,2-benzoquinones were prepared from catechol and the corresponding secondary amines in high yield in a single step using copper complex formation to stabilize the intermediate. The cytotoxicity of the products under various conditions was evaluated using the EMT-6 mammary carcinoma cell line, and antitumor activity was tested in the L1210 murine leukemia. The 4,5-diaziridinyl-1,2-benzoquinone was a more potent cytotoxic agent than diaziquone (AZQ) and was very effective against the L1210 leukemia. The azetidine, pyrrolidine, and diethylamine derivatives were not effective antitumor agents.
Huang
Z D
ZD
Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
Chen
Y N
YN
Menon
K
K
Teicher
B A
BA
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001388:Aziridines / Q000138:chemical synthesis / Q000494:pharmacology; D016227:Benzoquinones / Q000138:chemical synthesis* / Q000494:pharmacology*; D015687:Cell Hypoxia; D004354:Drug Screening Assays, Antitumor; D006863:Hydrogen-Ion Concentration; D007939:Leukemia L1210 / Q000188:drug therapy; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy; D051379:Mice; D008811:Mice, Inbred DBA; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001388:Aziridines; D016227:Benzoquinones