Synthesis and cytotoxicity evaluation of 6,11-dihydro-pyridazo- and 6,11-dihydro-pyrido[2,3-b]phenazine-6,11-diones

Hyun Jung Lee, Jin Sung Kim, Se Young Park, Myung Eun Suh, Hwa Jung Kim, Eun Kyung Seo, Chong Ock Lee

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The 6,11-dihydro-pyridazo[2,3-b]phenazine-6,11-dione and 6,11-dihydro-pyrido[2,3-b]phenazine-6,11-dione derivatives were synthesized from 6,7-dichloro-5,8-phthalazinedione and 6,7-dichloro-5,8-quinolinedione, respectively, producing a series of new anticancer drugs. The cytotoxic activities of the prepared compounds were evaluated by a SRB (Sulforhodamine B) assay against the following tumor cell lines: A459 (human lung), SK-OV-3 (human ovarian), SK-MEL-2 (human melanoma), XF498 (human CNS), and HCT 15 (human colon). Almost all the derivatives of the 6,11-dihydro-pyridazo[2[,3-b] phenazine-6,11-dione and 6,11-dihydro-pyrido[2,3-b]phenazine-6,11-dione, tetracyclic heteroquinone analogues with four or three nitrogen atoms, exhibited excellent cytotoxicity on almost all the human tumor cell lines tested. Specifically, 6,11-dihydro-pyridazo[2,3-b]phenazine-6,11-dione (4a) exhibited potent activity against all the tumor cell lines, and in particular, its cytotoxic effect against HCT 15 (ED50=0.004 μg/mL) was 25 times greater than that of doxorubicin (ED50=0.093 μg/mL).

Original languageEnglish
Pages (from-to)1623-1628
Number of pages6
JournalBioorganic and Medicinal Chemistry
Issue number7
StatePublished - 1 Apr 2004

Bibliographical note

Funding Information:
The authors wish to thank the Korea Science and Engineering Foundation for the financial support (R04-2000-000-00055-0) and the Korea Research Foundation Grant (KRF-2001-005-F00023).


  • 6,11-Dihydro-pyridazo[2,3-b]phenazine-6,11-dione
  • 6,11-Dihydro-pyrido[2,3-b] phenazine-6,11-diones
  • Cytotoxicity


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