Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
Bioorg Med Chem. 2011 Jan 1;19(1):275-86. doi: 10.1016/j.bmc.2010.11.030. Epub 2010 Dec 6.
A series of linear pyrrolo[1,2-b]isoquinoline derivatives was synthesized for antitumor evaluation. The preliminary antitumor studies reveal that both bis(hydroxymethyl) and their bis(alkylcarbamate) derivatives show significant antitumor activity in inhibiting various human tumor cell growth in vitro. 1,2-Bis(hydroxymethyl)-3-methyl-5,10-dihydropyrrolo[1,2-b]isoquinoline (20a) was selected for antitumor studies in animal models. The results show that this agent can induce complete tumor remission or significant suppression in nude mice bearing human breast (MX-1) xenograft and ovarian (SK-OV-3) xenografts, respectively. Alkaline agarose gel shifting assay showed that 20a is able to cross-link with DNA. Studies on the cell cycle inhibition revealed that this agent induces cell arrest at G2/M phase. The results warrant further antitumor investigation against other human tumor growth in animal models.
为了评估抗肿瘤活性，我们合成了一系列线性吡咯并[1,2-b]异喹啉衍生物。初步的抗肿瘤研究表明，双（羟甲基）及其双（烷基氨基甲酸酯）衍生物在体外均能显著抑制多种人肿瘤细胞的生长。1,2-双（羟甲基）-3-甲基-5,10-二氢吡咯并[1,2-b]异喹啉（20a）被选为抗肿瘤研究的候选药物。结果表明，该化合物能诱导荷人乳腺癌（MX-1）异种移植瘤和卵巢癌（SK-OV-3）异种移植瘤裸鼠完全消退或显著抑制肿瘤生长。碱性琼脂糖凝胶电泳迁移率改变实验表明，20a 能够与 DNA 交联。细胞周期抑制研究表明，该化合物诱导细胞在 G2/M 期停滞。这些结果证明了它在动物模型中对其他人类肿瘤生长的进一步抗肿瘤研究的价值。
