Amino substituted nitrogen heterocycle ureas as kinase insert domain containing receptor (KDR) inhibitors: Performance of structure-activity relationship approaches

Yilmaz H., Sizochenko N., Rasulev B., TOROPOV A., GÜZEL Y. , KUZ'MIN V., ...More

JOURNAL OF FOOD AND DRUG ANALYSIS, vol.23, no.2, pp.168-175, 2015 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 23 Issue: 2
  • Publication Date: 2015
  • Doi Number: 10.1016/j.jfda.2015.03.001
  • Title of Journal : JOURNAL OF FOOD AND DRUG ANALYSIS
  • Page Numbers: pp.168-175
  • Keywords: amino-substituted nitrogen, heterocyclic ureas, descriptors, KDR inhibitors, QSAR, SiRMS, SMILES, MOLECULAR-STRUCTURE, QSAR ANALYSIS, OPTIMAL DESCRIPTORS, RATE CONSTANTS, RANDOM FOREST, REPRESENTATION, PREDICTION, TOXICITY, SMILES, MUTAGENICITY

Abstract

A quantitative structure-activity relationship (QSAR) study was performed on a set of amino-substituted nitrogen heterocyclic urea derivatives. Two novel approaches were applied: (1) the simplified molecular input-line entry systems (SMILES) based optimal descriptors approach; and (2) the fragment-based simplex representation of molecular structure (SiRMS) approach. Comparison with the classic scheme of building up the model and balance of correlation (BC) for optimal descriptors approach shows that the BC scheme provides more robust predictions than the classic scheme for the considered pIC(50) of the heterocyclic urea derivatives. Comparison of the SMILES-based optimal descriptors and SiRMS approaches has confirmed good performance of both techniques in prediction of kinase insert domain containing receptor (KDR) inhibitory activity, expressed as a logarithm of inhibitory concentration (pIC50) of studied compounds. Copyright (C) 2015, Food and Drug Administration, Taiwan. Published by Elsevier Taiwan LLC. All rights reserved.