Synthesis and cytotoxicity evaluation of 2-amino- and 2-hidroxy-3-ethoxycarbonyl-N-substituted-benzo[f]indole-4,9-dione derivatives.
Reaction between 2,3-dichloronaphthoquinone (I) and ethyl cyanoacetate or diethyl malonate under different conditions gave the starting materials, 2-chloro-3-(alpha-cyano-alpha-ethoxycarbonyl-methyl)-1,4-naphthoquinone (A) or 2-chloro-3-(diethoxycarbonyl-methyl)-1,4-naphthoquinone (B). The 2-amino-3-ethoxycarbonyl-N-substituted-benzo[f]indole-4,9-dione derivatives [A-(1-10)] and 2-hydroxy-3-ethoxycarbonyl-N-substituted-benzo[f]indole-4,9-dione derivatives [B-(1-12)] were prepared from compounds A and B, respectively, by using various alkyl-, and arylamines. The cytotoxic activities of the prepared compounds were evaluated by 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). Many of the derivatives mentioned exhibited more potent cytotoxic effects against SK-OV-3 and XF498 than etoposide. Significantly, 2-amino-3-ethoxycarbonyl-N-(3-methyl-phenyl)-benzo[f]indole-4,9-dione (A-8) showed potent activity against all tumor cell lines, and in particular, its cytotoxic effect against SK-OV-3 was much higher than doxorubicin.
Lee
Hyun-Jung
HJ
Department of Medical Chemistry, College of pharmacy, Ewha Woman's University, Seoul 120-750, South Korea.
Suh
Myung-Eun
ME
Lee
Chong-Ock
CO
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D004396:Coloring Agents; D004317:Doxorubicin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D012235:Rhodamines; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D004396:Coloring Agents; D007202:Indicators and Reagents; D007211:Indoles; D012235:Rhodamines; C022027:lissamine rhodamine B; D005047:Etoposide; D004317:Doxorubicin