Synthesis and cytotoxicity evaluation of 2-amino- and 2-hidroxy-3-ethoxycarbonyl-N-substituted-benzo[f]indole-4,9-dione derivatives.
Synthesis and cytotoxicity evaluation of 2-amino- and 2-hidroxy-3-ethoxycarbonyl-N-substituted-benzo[f]indole-4,9-dione derivatives.
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DOI：
10.1016/s0968-0896(03)00062-2
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发表时间：
2003-04
影响因子：
3.5
通讯作者：
Hyun-Jung Lee;M. Suh;Chong‐Ock Lee
中科院分区：
文献类型：
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作者：
Hyun-Jung Lee;M. Suh;Chong‐Ock Lee
2，3-二氯萘醌（Ⅰ）与氰乙酸乙酯或丙二酸二乙酯在不同条件下反应，得到2-氯-3-（α-氰基-α-乙氧羰基-甲基）-1，4-萘醌（A）或2-氯-3-（二乙氧羰基-甲基）-1，4-萘醌（B）。2-氨基-3-乙氧羰基-N-取代的-苯并[f]吲哚-4，9-二酮衍生物[A-（1-10）]和2-羟基-3-乙氧羰基-N-取代的-苯并[f]吲哚-4，9-二酮衍生物[B-（1-12）]分别由化合物A和B通过使用各种烷基胺和芳基胺制备。通过SR B（磺酰罗丹明B）测定法评价制备的化合物对以下肿瘤细胞系的细胞毒性活性：A459（人肺）、SK-0 V-3（人卵巢）、SK-MEL-2（人黑素瘤）、XF 498（人CNS）和HCT 15（人结肠）。所提及的许多衍生物对SK-OV-3和XF 498的细胞毒作用比依托泊苷更强。值得注意的是，2-氨基-3-乙氧羰基-N-（3-甲基-苯基）-苯并[f]吲哚-4，9-二酮（A-8）显示出对所有肿瘤细胞系的有效活性，特别是其对SK-0 V-3的细胞毒性作用远高于多柔比星。
Reaction between 2,3-dichloronaphthoquinone (I) and ethyl cyanoacetate or diethyl malonate under different conditions gave the starting materials, 2-chloro-3-(α-cyano-α-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.