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QSAR study of heparanase inhibitors activity using artificial neural networks and Levenberg-Marquardt algorithm

Jalali Heravi, M ; Sharif University of Technology | 2008

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  1. Type of Document: Article
  2. DOI: 10.1016/j.ejmech.2007.04.014
  3. Publisher: 2008
  4. Abstract:
  5. A linear and non-linear quantitative structure-activity relationship (QSAR) study is presented for modeling and predicting heparanase inhibitors' activity. A data set that consisted of 92 derivatives of 2,3-dihydro-1,3-dioxo-1H-isoindole-5-carboxylic acid, furanyl-1,3-thiazol-2-yl and benzoxazol-5-yl acetic acids is used in this study. Among a large number of descriptors, four parameters classified as physico-chemical, topological and electronic indices are chosen using stepwise multiple regression technique. The artificial neural networks (ANNs) model shows superiority over the multiple linear regressions (MLR) by accounting 87.9% of the variances of antiviral potency of the heparanase inhibitors. This paper focuses on investigating the role of weight update functions in developing ANNs. Levenberg-Marquardt (L-M) algorithm shows a better performance compared with basic back propagation (BBP) and conjugate gradient (CG) algorithms. The accuracy of 4-3-1 L-M ANN model was illustrated using leave-one-out (LOO), leave-multiple-out (LMO) cross-validations and Y-randomization. The mean effect of descriptors and sensitivity analysis show that log P is the most important parameter affecting the inhibitory behavior of the molecules. © 2007 Elsevier Masson SAS. All rights reserved
  6. Keywords:
  7. 2,3 dihydro 1,3 dioxo 1h isoindole 5 carboxylic acid derivative ; Benzoxazol 5 yl acetic acid derivative ; Enzyme inhibitor ; Furanyl 1,3 thiazol 2 yl derivative ; Heparanase ; Unclassified drug ; Algorithm ; Artificial neural network ; Drug activity ; Drug structure ; IC 50 ; Physical chemistry ; Quantitative structure activity relation ; Sensitivity analysis ; Algorithms ; Enzyme Inhibitors ; Glucuronidase ; Models, Biological ; Neural Networks (Computer) ; Quantitative Structure-Activity Relationship ; Sensitivity and Specificity
  8. Source: European Journal of Medicinal Chemistry ; Volume 43, Issue 3 , 2008 , Pages 548-556 ; 02235234 (ISSN)
  9. URL: https://www.sciencedirect.com/science/article/abs/pii/S0223523407002000