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Synthesis and cytotoxicity evaluation of 6,11-dihydro-pyridazo- and 6,11-dihydro-pyrido[2,3-b]phenazine-6,11-diones
- Synthesis and cytotoxicity evaluation of 6,11-dihydro-pyridazo- and 6,11-dihydro-pyrido[2,3-b]phenazine-6,11-diones
- Lee H.-J.; Kim J.S.; Park S.-Y.; Suh M.-E.; Kim H.J.; Seo E.-K.; Lee C.-O.
- Ewha Authors
- 서명은; 김화정; 서은경; 김진성
- SCOPUS Author ID
- 서명은; 김화정; 서은경
- Issue Date
- Journal Title
- Bioorganic and Medicinal Chemistry
- vol. 12, no. 7, pp. 1623 - 1628
- SCI; SCIE; SCOPUS
- 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). © 2004 Elsevier Ltd. All rights reserved.
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