title: Classification of sphingosine kinase inhibitors using counter propagation artificial neural networks: A systematic route for designing selective SphK inhibitors.
abstract: Accurate and robust classification models for describing and predicting the activity of 330 chemicals that are sphingosine kinase 1 (SphK1) and/or sphingosine kinase 2 (SphK2) inhibitors were derived. The classification models developed in this work assist in finding selective subspaces in chemical space occupied by particular groups of SphK inhibitors. A combination of a genetic algorithm (GA) and a counter propagation artificial neural network (CPANN) was utilized to select the most efficient subsets of the molecular descriptors. The optimized models in this work reasonably separate active inhibitors of SphK1 from active SphK2 inhibitors. Generally, the CPANN models in this work were used to classify the compounds according to their therapeutic targets and activities. The simplicity of the chosen descriptors and their relative importance sheds some light on the structural features necessary to induce selective inhibitory activity to the studied molecules. The areas under the receiver operating characteristic (ROC) curves for the GA-CPANN models in this work were 0.934 and 0.922 for active SphK1 and SphK2 inhibitors, respectively. Generally, the results in this work suggest some important molecular features and pharmacophores that could help medicinal chemists develop selective and potent SphK inhibitors.
authors.affiliation: a Department of Chemistry , Yazd University , Yazd , Iran.
authors.forename: M S
authors.initials: MS
authors.lastname: Neiband
authors.affiliation: b Chemometrics and Chemoinformatics Laboratory , Tarbiat Modares University , Tehran , Iran.
authors.forename: A
authors.initials: A
authors.lastname: Mani-Varnosfaderani
authors.affiliation: a Department of Chemistry , Yazd University , Yazd , Iran.
authors.forename: A
authors.initials: A
authors.lastname: Benvidi
mesh_terms: D000465:Algorithms; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003198:Computer Simulation; D055808:Drug Discovery / Q000379:methods; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000145:classification* / Q000494:pharmacology*; D016571:Neural Networks, Computer; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors*; D012372:ROC Curve; D000099157:Sphingosine Kinase
chemical_list: D004791:Enzyme Inhibitors; D017853:Phosphotransferases (Alcohol Group Acceptor); D000099157:Sphingosine Kinase
keywords: Sphingosine kinases; chemical space; counter propagation artificial neural network; genetic algorithm; selective drug discovery