Sección de síntesis, Departamento de Química Orgánica y Farmacéutica, University of Navarra, Irunlarrea, 1, E-31008 Pamplona, Spain.
Eur J Med Chem. 2012 Jan;47(1):283-98. doi: 10.1016/j.ejmech.2011.10.056. Epub 2011 Nov 6.
The synthesis, cytotoxic activities and selectivities of 35 derivatives related to quinazoline and pyrido[2,3-d]pyrimidine are described. The synthesized compounds were screened in vitro against four tumoral cell lines - leukemia (CCRF-CEM), colon (HT-29), lung (HTB-54) and breast (MCF-7) - and two cell lines derived from non-malignant cell lines, one mammary (184B5) and one from bronchial epithelium (BEAS-2B). MCF-7 and HTB-54 were the most sensitive cell lines with GI(50) values below 10μM for eleven and ten compounds, respectively. Two compounds (2o and 3a) were identified that evoked a marked cytotoxic effect in all cell lines tested and one compound, 7h, was potent and selective against MCF-7. A preliminary study into the mechanism of the potent derivatives 2o, 3a and 7h indicated that the cytotoxic activities of these compounds might be mediated by inducing cell death without affecting cell cycle phases.
描述了 35 种与喹唑啉和吡啶并[2,3-d]嘧啶相关的衍生物的合成、细胞毒性活性和选择性。合成的化合物在体外对四种肿瘤细胞系——白血病（CCRF-CEM）、结肠（HT-29）、肺（HTB-54）和乳腺（MCF-7）以及源自非恶性细胞系的两种细胞系——一种乳腺（184B5）和一种支气管上皮（BEAS-2B）进行了筛选。MCF-7 和 HTB-54 是最敏感的细胞系，有 11 种和 10 种化合物的 GI（50）值低于 10μM。鉴定出两种化合物（2o 和 3a），它们在所有测试的细胞系中均能引起明显的细胞毒性作用，一种化合物 7h 对 MCF-7 具有强大的选择性。对强效衍生物 2o、3a 和 7h 的机制的初步研究表明，这些化合物的细胞毒性活性可能是通过诱导细胞死亡而不影响细胞周期阶段来介导的。
