Monte Carlo method based QSAR modeling of maleimide derivatives as glycogen synthase kinase-3β inhibitors

被引:27
作者
Zivkovic, Jelena V. [1 ]
Trutic, Natasa V. [1 ]
Veselinovic, Jovana B. [1 ]
Nikolic, Goran M. [1 ]
Veselinovic, Aleksandar M. [1 ]
机构
[1] Univ Nis, Dept Chem, Fac Med, Nish 18000, Serbia
关键词
QSAR; SMILES; Monte Carlo method; Glycogen synthase kinase-3 beta inhibitors; CORAL software; Maleimide derivatives; GSK-3-BETA INHIBITORS; SELECTIVE INHIBITORS; GSK3; INHIBITORS; SMILES NOTATION; POTENT; DESCRIPTORS; DISCOVERY; VALIDATION; CORAL; TOXICITY;
D O I
10.1016/j.compbiomed.2015.07.004
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
The Monte Carlo method was used for QSAR modeling of maleimide derivatives as glycogen synthase kinase-3 beta inhibitors. The first QSAR model was developed for a series of 74 3-anilino-4-arylmaleimide derivatives. The second QSAR model was developed for a series of 177 maleimide derivatives. QSAR models were calculated with the representation of the molecular structure by the simplified molecular input-line entry system. Two splits have been examined: one split into the training and test set for the first QSAR model, and one split into the training, test and validation set for the second. The statistical quality of the developed model is very good. The calculated model for 3-anilino-4-arylmaleimide derivatives had following statistical parameters: r(2)=0.8617 for the training set; r(2)=0.8659, and r(m)(2)=0.7361 for the test set. The calculated model for maleimide derivatives had following statistical parameters: r(2)=0.9435, for the training, r(2)=0.9262 and r(m)(2)=0.8199 for the test and r(2)=0.8418, r((av)) m(2)=7469 and Delta r(m)(2)=0.1476 for the validation set. Structural indicators considered as molecular fragments responsible for the increase and decrease in the inhibition activity have been defined. The computer-aided design of new potential glycogen synthase kinase-3 beta inhibitors has been presented by using defined structural alerts. (C) 2015 Elsevier Ltd. All rights reserved.
引用
收藏
页码:276 / 282
页数:7
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