6533b85bfe1ef96bd12bb698

RESEARCH PRODUCT

Synthesis and cytotoxicity of 6,11-Dihydro-pyrido- and 6,11-Dihydro-benzo[2,3-b]phenazine-6,11-dione derivatives

Myung-eun SuhDieter SchollmeyerYoung-shin KimSe-young ParkHyun Jung LeeChong-ock Lee

subject

StereochemistryClinical BiochemistryPhenazinePharmaceutical ScienceAntineoplastic AgentsCrystallography X-RayBiochemistryChemical synthesisInhibitory Concentration 50Structure-Activity Relationshipchemistry.chemical_compoundDrug DiscoveryTumor Cells CulturedNucleophilic substitutionHumansStructure–activity relationshipCytotoxicityMolecular BiologyMolecular StructureOrganic ChemistryIn vitroQuinonechemistryDoxorubicinCell cultureQuinolinesPhenazinesMolecular MedicineDrug Screening Assays AntitumorNaphthoquinones

description

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.

yearjournalcountryeditionlanguage
2003-04-01Bioorganic & Medicinal Chemistry
https://doi.org/10.1016/s0968-0896(03)00028-2