title: Therapeutic index modeling and predictive QSAR of novel thiazolidin-4-one analogs against Toxoplasma gondii.
abstract: The main idea of this study was to find predictive quantitative structure-activity relationships (QSAR) for the therapeutic index of 68 thiazolidin-4-one analogs against Toxoplasma gondii. Multivariate adaptive regression spline (MARS) together with Monte-Carlo (MC) sampling was proposed as a reliable descriptor subset selection strategy. Basis functions and knot points are also determined for each selected descriptor using generalized cross validation after frequency analysis. Least squares-support vector regression (LS-SVR) with optimized hyper-parameters was employed as mapping tool due to its promising empirical performance. The models were validated and tested through the use of the external prediction set of compounds, leave-one-out and leave-many-out cross validation methods, applicability domain analysis and Y-randomization. The robustness and accuracy of the QSAR models were confirmed by the satisfactory statistical parameters for the experimentally reported dataset (R(2)p=0.853, Q(2)LOO=0.785, R(2)L20%O=0.742 and r(2)m=0.715) and low standard error values (RMSEp=0.208, RMSELOO=0.321 and RMSEL20%O=0.376). The comprehensive analysis carried out in the present contribution using the proposed strategy can provide a considerable basis for the design and development of novel drug-like molecules against T.gondii.
authors: Department of Science, Babol University of Technology, Babol 47148-71167, Mazandaran, Iran. Electronic address: asadollahi@nit.ac.ir.
authors: M
authors: M
authors: Asadollahi-Baboli
authors: Department of Chemistry, Tarbiat Modares University, Tehran 14115-175, Iran.
authors: A
authors: A
authors: Mani-Varnosfaderani
mesh_terms: D005544:Forecasting; D008958:Models, Molecular; D009010:Monte Carlo Method; D021281:Quantitative Structure-Activity Relationship; D045162:Thiazolidinediones / Q000737:chemistry* / Q000494:pharmacology*; D014122:Toxoplasma / Q000187:drug effects* / Q000502:physiology
chemical_list: D045162:Thiazolidinediones
keywords: Monte-Carlo sampling; Multivariate adaptive regression spline; Support vector machine; Therapeutic index; Toxoplasma gondii