^(153)Sm骨肿瘤治疗药物配体结构与生物活性相关性研究  

STUDY OF QSAR FOR ^(153)Sm COMPLEXES AS BONE SEEKING AGENT

作　　者：魏洪源[1] 罗顺忠[1] 刘国平[1] 杨玉青[1] 蒋树斌[1] 

机构地区：[1]中国工程物理研究院核物理与化学研究所,四川绵阳621900

出　　处：《核化学与放射化学》2003年第2期81-85,共5页Journal of Nuclear and Radiochemistry

基　　金：国家自然科学基金资助项目(29971027);中国工程物理研究院核物理与化学研究所所长基金资助项目(703)

摘　　要：使用MaterialStudio2.0分子模拟软件对17个153Sm骨肿瘤治疗药物配体分子进行了分子建模,用分子力学和分子动力学方法进行了结构优化,找到了最优构象。使用半经验分子轨道软件包Vamp计算了配体分子在水溶液中的单点能,获得了LUMO,HOMO轨道能级、偶极矩、离域能、生成焓等微观结构参数。在此基础上用QSAR分析软件TsarTM3.3,进行了153Sm配合物的生物活性与配体分子结构的定量关联(活性参数选用注射2h后骨的放射性摄取率BU/(%·g-1)),建立了有一定预报能力的QSAR方程。The molecular modeling software, Material Studio 2.0, is employed to build the molecular models for the 17 153Smlabelled boneseeking radiopharmaceuticals. Their structures are first optimized with molecular mechanics and then the predominant conformations are found by using molecular dynamics. Energies of the 17 ligands in aqueous solution are calculated by the semiempirical orbital computation software package Vamp. A series of microscopic parameters such as LUMO and HOMO energies, delocalization energies and heat of formation are obtained. By choosing ADME violation number x10, surface area x14, and HOMO energy x20 as descriptors, a satisfactory QSAR equation is found by using QSAR analysis software TsarTM3.3 for bone uptake(BU/(%·g-1))2 h post injection. The equation is BU=-29.39/x10+12 455/x14-790.9/x20-82.38 with n=15, r=0.960 0, s=5.020, F=0, r2(CV)=0.590 4.

关 键 词：^153SM 骨肿瘤 治疗药物 配体结构 生物活性 相关性 作用机理 钐 

分 类 号：R979.1[医药卫生—药品] R914[医药卫生—药学]