Pharmacophore Modelling and 4D-QSAR Study of Ruthenium(II) Arene Complexes as Anticancer Agents (Inhibitors) by Electron Conformational-Genetic Algorithm Method
[ X ]
Tarih
2018
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Bentham Science Publ Ltd
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Objective: The EC-GA method was employed in this study as a 4D-QSAR method, for the identification of the pharmacophore (Pha) of ruthenium(II) arene complex derivatives and quantitative prediction of activity. Methods: The arrangement of the computed geometric and electronic parameters for atoms and bonds of each compound occurring in a matrix is known as the electron-conformational matrix of congruity (ECMC). It contains the data from HF/3-21G level calculations. Compounds were represented by a group of conformers for each compound rather than a single conformation, known as fourth dimension to generate the model. ECMCs were compared within a certain range of tolerance values by using the EMRE program and the responsible pharmacophore group for ruthenium(II) arene complex derivatives was found. For selecting the sub-parameter which had the most effect on activity in the series and the calculation of theoretical activity values, the non-linear least square method and genetic algorithm which are included in the EMRE program were used. In addition, compounds were classified as the training and test set and the accuracy of the models was tested by cross-validation statistically. Results: The model for training and test sets attained by the optimum 10 parameters gave highly satisfactory results with R-training(2) = 0.817, q(2) = 0.718 and SEtraining = 0.066, q(2) (ext1) = 0.867, q(2) (ext2) = 0.849, q(2) (ext3) = 0.895, ccc(tr) = 0.895, ccc(test) = 0.930 and cc(call) = 0.905. Conclusion: Since there is no 4D-QSAR research on metal based organic complexes in the literature, this study is original and gives a powerful tool to the design of novel and selective ruthenium(II) arene complexes.
Açıklama
Anahtar Kelimeler
4D-QSAR, ruthenium(II) arene complexes, pharmacophore, electron conformational-genetic algorithm method
Kaynak
Current Computer-Aided Drug Design
WoS Q Değeri
Q4
Scopus Q Değeri
Q3
Cilt
14
Sayı
1
