QSAR studies of copper azamacrocycles and thiosemicarbazones: MM3 parameter development and prediction of biological properties.
QSAR studies of copper azamacrocycles and thiosemicarbazones: MM3 parameter development and prediction of biological properties.
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铜氮杂大环和缩氨基硫脲的 QSAR 研究：MM3 参数开发和生物特性预测。
DOI：
10.1021/jm0501376
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发表时间：
2005
影响因子：
7.3
通讯作者：
Reichert,DavidE
中科院分区：
文献类型：
--
作者：
Wolohan,Peter;Yoo,Jeongsoo;Welch,MichaelJ;Reichert,DavidE
结合晶体结构和从头计算方法，利用遗传算法(GA)对特定的铜金属−配位体的力场参数进行计算。这些新参数得到的结果与实验和之前报道的铜金属−配体琥珀力场参数很好地吻合。然后利用MM3参数建立了几个定量结构构效关系(Quantity Structure−Activity Relationship，QSAR)模型。利用32个铜(II)放射性金属络合物和6个简单分子描述符的训练集，成功地建立了预测几类铜(II)螯合配体的亲脂性(LogPow)的QSAR。定量构效关系的预测值与实验值之间存在较好的相关性，相关系数分别为0.95和0.92。当应用于11个铜(II)络合物的外部测试集时，QSAR具有很高的准确性；采用留一法交叉验证分析，R2=0.93，aq2=0.91。另外还开发了一些QSAR模型来预测一组较小的铜(II)双(缩氨基硫脲)络合物的生物分布。
Genetic algorithms (GA) were used to develop specific copper metal−ligand force field parameters for the MM3 force field, from a combination of crystallographic structures and ab initio calculations. These new parameters produced results in good agreement with experiment and previously reported copper metal−ligand parameters for the AMBER force field. The MM3 parameters were then used to develop several quantitative structure−activity relationship (QSAR) models. A successful QSAR for predicting the lipophilicity (logPow) of several classes of Cu(II)-chelating ligands was built using a training set of 32 Cu(II) radiometal complexes and 6 simple molecular descriptors. The QSAR exhibited a correlation between the predicted and experimental logPowwith anr2= 0.95,q2= 0.92. When applied to an external test set of 11 Cu(II) complexes, the QSAR preformed with great accuracy;r2= 0.93 and aq2= 0.91 utilizing a leave-one-out cross-validation analysis. Additional QSAR models were developed to predict the biodistribution of a smaller set of Cu(II) bis(thiosemicarbazone) complexes.