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

doi:10.1016/j.bmc.2004.01.029

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

Department of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

50 Scopus citations

Abstract

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 language	English
Pages (from-to)	1623-1628
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry
Volume	12
Issue number	7
DOIs	https://doi.org/10.1016/j.bmc.2004.01.029
State	Published - 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).

Keywords

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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10.1016/j.bmc.2004.01.029

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@article{cb0ebd926aa84aa3960eed0a1ffb0c5b,

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

abstract = "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).",

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

author = "Lee, {Hyun Jung} and Kim, {Jin Sung} and Park, {Se Young} and Suh, {Myung Eun} and Kim, {Hwa Jung} and Seo, {Eun Kyung} and Lee, {Chong Ock}",

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). ",

year = "2004",

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doi = "10.1016/j.bmc.2004.01.029",

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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).

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KW - 6,11-Dihydro-pyrido[2,3-b] phenazine-6,11-diones

KW - Cytotoxicity

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DO - 10.1016/j.bmc.2004.01.029

M3 - Article

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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 -

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

Abstract

Bibliographical note

Keywords

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