title: Models for H₃ receptor antagonist activity of sulfonylurea derivatives.
abstract: The histamine H₃ receptor has been perceived as an auspicious target for the treatment of various central and peripheral nervous system diseases. In present study, a wide variety of 60 2D and 3D molecular descriptors (MDs) were successfully utilized for the development of models for the prediction of antagonist activity of sulfonylurea derivatives for histamine H₃ receptors. Models were developed through decision tree (DT), random forest (RF) and moving average analysis (MAA). Dragon software version 6.0.28 was employed for calculation of values of diverse MDs of each analogue involved in the data set. The DT classified and correctly predicted the input data with an impressive non-error rate of 94% in the training set and 82.5% during cross validation. RF correctly classified the analogues into active and inactive with a non-error rate of 79.3%. The MAA based models predicted the antagonist histamine H₃ receptor activity with non-error rate up to 90%. Active ranges of the proposed MAA based models not only exhibited high potency but also showed improved safety as indicated by relatively high values of selectivity index. The statistical significance of the models was assessed through sensitivity, specificity, non-error rate, Matthew's correlation coefficient and intercorrelation analysis. Proposed models offer vast potential for providing lead structures for development of potent but safe H₃ receptor antagonist sulfonylurea derivatives.
authors.affiliation: Faculty of Pharmaceutical Sciences, Pt. B. D. Sharma University of Health Sciences, Rohtak 124001, India.
authors.forename: Naveen
authors.initials: N
authors.lastname: Khatri
authors.affiliation: Faculty of Pharmaceutical Sciences, Pt. B. D. Sharma University of Health Sciences, Rohtak 124001, India. Electronic address: madan_ak@yahoo.com.
authors.forename: A K
authors.initials: AK
authors.lastname: Madan
mesh_terms: D003198:Computer Simulation; D003663:Decision Trees; D006633:Histamine Antagonists / Q000737:chemistry*; D006801:Humans; D008956:Models, Chemical; D021281:Quantitative Structure-Activity Relationship; D018100:Receptors, Histamine H3 / Q000737:chemistry*; D013453:Sulfonylurea Compounds / Q000737:chemistry*
chemical_list: D006633:Histamine Antagonists; D018100:Receptors, Histamine H3; D013453:Sulfonylurea Compounds
keywords: Decision tree; Dragon software; Histamine H(3) receptor antagonist; Moving average analysis; Random forest; Sulfonylurea derivatives