Yuriev E, Orbell J D
Department of Environmental Management, Victoria University of Technology, Melbourne, Australia.
J Comput Aided Mol Des. 1996 Dec;10(6):589-606. doi: 10.1007/BF00134182.
A repulsive energy strategy has been employed in an attempt to delineate the steric contribution to the biological profile of a variety of platinum-am(m)ine complexes. Thus, relative steric descriptors have been calculated for the amine ligands themselves by the Ligand Repulsive Energy (LRE) methodology. This has been extended to a Complex Repulsive Energy (CRE) strategy whereby the steric requirements of the approach of a metal complex to a site on a target molecule may be evaluated. Specifically, the monodentate approach of a variety of platinum-am(m)ine complexes to the N7 site of a guanine moiety has been considered. The steric descriptors thus obtained have been used in QSAR analysis, resulting in improved regression equations. Attempts have also been made to relate the above descriptors to various biological indicators for given series of complexes. These investigations suggest an optimum steric requirement for minimum toxicity, which could aid in the rational design of such agents.
为了描述各种铂胺配合物的空间效应对其生物学特性的贡献，采用了一种斥力能量策略。因此，通过配体斥力能量（LRE）方法计算了胺配体自身的相对空间描述符。这已扩展为一种配合物斥力能量（CRE）策略，据此可以评估金属配合物接近目标分子上某一位置的空间需求。具体而言，考虑了各种铂胺配合物对鸟嘌呤部分N7位点的单齿接近方式。由此获得的空间描述符已用于定量构效关系（QSAR）分析，得到了改进的回归方程。还尝试将上述描述符与给定系列配合物的各种生物学指标联系起来。这些研究表明了最小毒性的最佳空间需求，这有助于此类药物的合理设计。
