TY - JOUR
T1 - Synthesis and cytotoxicity evaluation of 6,11-dihydro-pyridazo- and 6,11-dihydro-pyrido[2,3-b]phenazine-6,11-diones
AU - Lee, Hyun Jung
AU - Kim, Jin Sung
AU - Park, Se Young
AU - Suh, Myung Eun
AU - Kim, Hwa Jung
AU - Seo, Eun Kyung
AU - Lee, Chong Ock
N1 - 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).
PY - 2004/4/1
Y1 - 2004/4/1
N2 - 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).
AB - 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).
KW - 6,11-Dihydro-pyridazo[2,3-b]phenazine-6,11-dione
KW - 6,11-Dihydro-pyrido[2,3-b] phenazine-6,11-diones
KW - Cytotoxicity
UR - http://www.scopus.com/inward/record.url?scp=1542509347&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2004.01.029
DO - 10.1016/j.bmc.2004.01.029
M3 - Article
C2 - 15028255
AN - SCOPUS:1542509347
SN - 0968-0896
VL - 12
SP - 1623
EP - 1628
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 7
ER -