Graduate Institute of Pharmaceutical Chemistry, China Medical University, No. 91 Hsueh-Shih Road, Taichung 40402, Taiwan ROC.
Eur J Med Chem. 2013 Aug;66:466-79. doi: 10.1016/j.ejmech.2013.06.012. Epub 2013 Jun 18.
We synthesized and evaluated a series of 2,4-disubstituted furo[3,2-b]indole derivatives for anticancer activity and established the structure-activity relationships (SARs) of these compounds. Among all tested compounds, we found (5-((2-(hydroxymethyl)-4H-furo[3,2-b]indol-4-yl)methyl)furan-2-yl)methanol (10a) to be the most promising agent. In screening against NCI-60 human tumor cell lines, 10a exhibited highly selective anticancer activity and significant inhibitory activity against A498 renal cancer cells. Our COMPARE analysis results suggest that the 10a fingerprint is similar to that of NSC-754549, which is an isostere of YC-1. We further confirmed the significant antitumor activity of compound 10a with tests in the A498 xenograft nude mice model. Therefore, compound 10a should be further developed as a new drug candidate for treating renal cancer.
我们合成并评估了一系列 2,4-二取代呋喃并[3,2-b]吲哚衍生物的抗癌活性，并建立了这些化合物的构效关系（SARs）。在所有测试的化合物中，我们发现（5-((2-(羟甲基)-4H-呋喃并[3,2-b]吲哚-4-基)甲基)呋喃-2-基)甲醇（10a）是最有前途的药物。在对 NCI-60 人肿瘤细胞系的筛选中，10a 表现出高度的选择性抗癌活性和对 A498 肾癌细胞的显著抑制活性。我们的 COMPARE 分析结果表明，10a 的指纹图谱与 NSC-754549 的指纹图谱相似，后者是 YC-1 的等排体。我们进一步用 A498 异种移植裸鼠模型的试验证实了化合物 10a 的显著抗肿瘤活性。因此，化合物 10a 应作为治疗肾癌的新药候选物进一步开发。
