Kamano Y, Kotake A, Hashima H, Inoue M, Morita H, Takeya K, Itokawa H, Nandachi N, Segawa T, Yukita A, Saitou K, Katsuyama M, Pettit G R
Faculty of Science, Kanagawa University, Hiratsuka, Japan.
Bioorg Med Chem. 1998 Jul;6(7):1103-15. doi: 10.1016/s0968-0896(98)00067-4.
The toad poison bufadienolides including natural and derivatized compounds were tested for their cytotoxic effects on primary liver carcinoma cells PLC/PRF/5 and their structure-cytotoxic activity relationships were studied. For this study, a ligand-binding model was developed by using a pharmacophore mapping program, Distance Comparisons (DISCO). The structural features that are common to the 3D structures of active bufadienolides were identified to provide approach to a 3D QSAR method by using Comparative Molecular Field Analysis (CoMFA) study and to correlate the steric and electrostatic fields of the molecules to their activities. A valuable model which enables prediction of their activities was obtained from the CoMFA analysis, which may be employed for the drug designs of new bufadienolide analogues.
对包括天然和衍生化合物在内的蟾蜍毒素类强心甾烯蟾毒配基进行了对原发性肝癌细胞PLC/PRF/5的细胞毒性作用测试，并研究了它们的结构-细胞毒性活性关系。在本研究中，通过使用药效团映射程序Distance Comparisons（DISCO）开发了一种配体结合模型。确定了活性强心甾烯蟾毒配基三维结构的共同结构特征，以便通过比较分子场分析（CoMFA）研究为三维定量构效关系方法提供途径，并将分子的空间和静电场与其活性相关联。通过CoMFA分析获得了一个能够预测其活性的有价值模型，该模型可用于新的强心甾烯蟾毒配基类似物的药物设计。
