Synthesis of pyridino[2,3-f]indole-4,9-dione and 6,7-disubstituted quinoline-5,8-dione derivatives and evaluation on their cytotoxic activity.
We report upon the synthesis of the following derivatives: N-substituted-pyridino[2,3-f]indole-4,9-dione, and 6-(alpha-diethoxycarbonyl-methyl)-7-substituted-amino-quinoline-5,8-dione, which contain the active quinoline-5,8-dione (VII) moiety. The cytotoxic activities of these compounds have been tested in SRB (SulfoRhodamine B) assays against the cancer cell lines of A-549 (human lung cancer), SK-MEL-2 (human melanoma cancer), SK-OV-3 (human ovarian cancer), XF-498 (human brain cancer) and HCT 15 (human colon cancer). The compound, N-benzyl-3-ethoxycarbonyl-2-hydroxy-pyridino[2,3-f]indole-4,9-dione (A-9), also showed higher activity than cis-platin. The highest level of cytotoxic activity in these human tumor cell lines was observed in the compound 6-(alpha-diethoxycarbonyl-methyl)-7-(2-methyl-phenylamino)-quinoline-5,8-dione (B-3).
Suh
M E
ME
Division of Medicinal Chemistry, College of Pharmacy, Ewha Womans University, 120-750, Seoul, South Korea. suh@mm.ewha.ac.kr
Park
S Y
SY
Lee
C O
CO
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D014176:Protein Biosynthesis; D011506:Proteins / Q000187:drug effects; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015363:Quinolones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011809:Quinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D007211:Indoles; D011506:Proteins; D011725:Pyridines; D015363:Quinolones; D011809:Quinones