Chang Chih-Yi, Chuang Hsun-Yueh, Lee Hsueh-Yun, Yeh Teng-Kuang, Kuo Ching-Chuan, Chang Chi-Yen, Chang Jang-Yang, Liou Jing-Ping
School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan, ROC.
Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli 350, Taiwan, ROC.
Eur J Med Chem. 2014 Apr 22;77:306-14. doi: 10.1016/j.ejmech.2014.02.061. Epub 2014 Mar 1.
2-Hydroxy-3,4,5-trimethoxybenzophenones (8-16) manifest pseudo-ring formation involving intramolecular hydrogen bonding of the 2-OH and the carbonyl group. Among the synthetic products described in this report, (3-hydroxy-4-methoxyphenyl)(2-hydroxy-3,4,5-trimethoxyphenyl)-methanone (14) and (3-amino-4-methoxyphenyl)(2-hydroxy-3,4,5-trimethoxy-phenyl)methanone (16) exhibit significant antiproliferative activity against KB cells with IC50 values of 11.1 and 11.3 nM, respectively. These two compounds also displayed tubulin affinity comparable to that of combretastatin A-4. In studies with human umbilical vein endothelial cells, compounds 14 and 16 revealed concentration-dependent vascular-disrupting properties. The results support the rationale of the pseudo-ring concept and suggest further investigation of A-ring modification in these benzophenones.
2-羟基-3,4,5-三甲氧基二苯甲酮（8-16）呈现出涉及2-OH与羰基分子内氢键的假环形成。在本报告所述的合成产物中，（3-羟基-4-甲氧基苯基）（2-羟基-3,4,5-三甲氧基苯基）甲酮（14）和（3-氨基-4-甲氧基苯基）（2-羟基-3,4,5-三甲氧基苯基）甲酮（16）对KB细胞表现出显著的抗增殖活性，IC50值分别为11.1和11.3 nM。这两种化合物还表现出与康普瑞他汀A-4相当的微管蛋白亲和力。在对人脐静脉内皮细胞的研究中，化合物14和16显示出浓度依赖性的血管破坏特性。这些结果支持了假环概念的基本原理，并建议对这些二苯甲酮的A环修饰进行进一步研究。
