Synthesis and cytotoxicity of 6,11-dihydro-pyrido- and 6,11-dihydro-benzo[2,3-b]phenazine-6,11-dione derivatives.
6,11-Dihydro-pyrido[2,3-b]phenazine-6,11-diones and 6,11-dihydro-benzo[2,3-b]phenazine-6,11-diones were synthesized from 6,7-dichloro-5,8-quinolinedione and 2,3-dichloro-1,4-naphthoquinone. The study on the cytotoxicity on these products revealed that the pyridophenazinediones, tetracyclic heteroquinone analogues with three nitrogen atoms exhibited a high cytotoxicity on several human tumor cell lines. Compound 9c and 9e showed in vitro antitumor activity comparable or superior to doxorubicin against the human ovarian tumor cells (SK-OV-3) and the human CNS cells (XF 498). The IC(50) value for compound 9e was 0.06 microM against the human CNS cells (XF 498), which was 2.6 times higher than that (0.16 microM) of doxorubicin. In addition, the X-ray crystallographic analysis of two phenazinedione derivatives (9b,c) showed clearly the exact position of the nucleophilic substitution of 6,7-dichloro-5,8-quinolinedione.
Kim
Young-Shin
YS
Division of Medicinal Chemistry, College of Pharmacy, Ewha Woman's University, Seoul 120-750, South Korea.
Park
Se-Young
SY
Lee
Hyun-Jung
HJ
Suh
Myung-Eun
ME
Schollmeyer
Dieter
D
Lee
Chong-Ock
CO
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004317:Doxorubicin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009285:Naphthoquinones / Q000737:chemistry; D010619:Phenazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011804:Quinolines / Q000737:chemistry; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D009285:Naphthoquinones; D010619:Phenazines; D011804:Quinolines; D004317:Doxorubicin