Synthesis and cytotoxicity evaluation of pyridin[2,3-f]indole-2,4,9-trione and benz[f]indole-2,4,9-trione derivatives.
3-Ethoxycarbonyl-3-methyl-1N-substrituted-2,3-dihydro-pyridin[2,3-f]indole-2,4,9-trione [9(a-d)] and 3-ethoxycarbonyl-3-methyl-N-substrituted-2,3-dihydro-benz[f]indole-2,4,9-trione [10(a-i)] derivatives were synthesized from 7-chloro-6-(1,1-diethoxycarbonyl-ethyl)-5,8-quinolinedione (7) and 2-chloro-3-(1,1-diethoxycarbonyl-ethyl)-1,4-naphthoquinone (8), respectively, using a variety of alkyl- and arylamines. The cytotoxic activities of the synthesized compounds were evaluated by a Sulforhodamine B (SRB) assay against the following tumor cell lines: A459 (human non-small cell lung), SK-OV-3 (human ovarian), SK-MEL-2 (human melanoma), XF498 (human CNS), and HCT 15 (human colon). Almost all the derivatives mentioned above had a more potent cytotoxic effect against SK-OV-3 than etoposide. In particular, 3-ethoxycarbonyl-3-methyl-N-(4-aminophenyl)-2,3-dihydro-benz[f]indole-2,4,9-trione (10h) exhibited greater activity against all the tumor cell lines, and its cytotoxic effect against SK-OV-3 was especially higher than doxorubicin.
Lee
Hyun Jung
HJ
Department of Medicinal Chemistry, College of Pharmacy, Ewha Woman's University, 120-750 Seoul, South Korea.
Park
So Young
SY
Kim
Jin Sung
JS
Song
Hyun Min
HM
Suh
Myung Eun
ME
Lee
Chong Ock
CO
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001555:Benzene Derivatives / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D001555:Benzene Derivatives; D007211:Indoles; D011725:Pyridines; D005047:Etoposide; D004317:Doxorubicin