Laboratory of Synthetic Organic Chemistry, Department of Chemistry, University of Patras, GR-265 04 Patras, Greece.
Eur J Med Chem. 2011 Feb;46(2):721-37. doi: 10.1016/j.ejmech.2010.12.008. Epub 2010 Dec 14.
Acitretin analogs, incorporating changes in the lipophilic part, were efficiently synthesized from commercially available aromatic aldehydes or methyl ketones using the Wittig or Horner-Wadsworth-Emmons reaction. Their antiproliferative activity was evaluated against human breast MCF-7 epithelial cells. Analogs 3, 4, 8 and 11 exhibited strong, dose-dependent, antiproliferative activity on the tested cell line. Analog 3, incorporating three methoxy groups in the aromatic ring, exhibited the strongest inhibitory effect at 10 μM. High-level all electron conventional ab initio and density functional theory quantum chemical calculations were performed to obtain the molecular structure, electron charge distribution and polarization properties of all compounds of interest in this work. The most active analogs were planar and were characterized by larger dipole moments than the other synthesized molecules. Another factor of importance to the analysis of the activity of these molecules is the dipole polarizability.
阿维 A 类似物，通过对亲脂部分的改变，采用 Wittig 或 Horner-Wadsworth-Emmons 反应，可从市售的芳香醛或甲基酮有效地合成。它们对人乳腺癌 MCF-7 上皮细胞的增殖活性进行了评估。类似物 3、4、8 和 11 对测试的细胞系表现出强的、剂量依赖性的增殖抑制活性。类似物 3，在芳环中含有三个甲氧基，在 10μM 时表现出最强的抑制作用。进行了高级全电子传统从头算和密度泛函理论量子化学计算，以获得本工作中所有感兴趣化合物的分子结构、电子电荷分布和极化性质。最活跃的类似物是平面的，其偶极矩大于其他合成分子。对这些分子活性进行分析的另一个重要因素是偶极极化率。
