NP TLC DATA IN STRUCTURE-ACTIVITY RELATIONSHIP STUDY OF SELECTED COMPOUNDS WITH ACTIVITY ON DOPAMINERGIC, SEROTONINERGIC, AND MUSCARINIC RECEPTORS

Abstract

The available information on ligand-binding sites within the metabotropic receptors allows us to choose and apply chemical elements of the biological environment in the chromatographic analysis, which are responsible for formation of the drug-receptor complex. This information provides the opportunity to form analytical and statistical models of interactions between the drugs studied and dopaminergic, serotoninergic, and muscarinic receptors. Simple analytical models for predicting the direction of potential activity within these receptors with the use of chromatographic data and calculated physicochemical parameters were presented. The statistical tool used in this study was Stepwise Discriminant Analysis (SDA). The joint element of simulated environment interactions between various compounds and a biological goal is aspartic acid. The NP TLC plates, impregnated with a solution of aspartic acid (L-Asp), were used in two developing solvents as metabotropic receptors interaction models. The 33 selected drugs were divided into three groups of activity. The following group codes were assigned to them a priori: D, 5HT, and M (for compounds with activity on dopaminergic, serotoninergic, and muscarinic receptors, respectively). The presented discriminant models based on biochromatographic studies and physicochemical data are an efficient tool in the SAR analysis for initial prediction of compound activity direction within selected receptors.

Keywords:

• biochromatography
• metabotropic receptors
• molecular descriptors
• stepwise discriminant analysis
• structure-activity relationship
• thin layer chromatography

ACKNOWLEDGMENT

This work has been supported by an internal grant of the Medical University of Lodz, Poland (Project No. 502-13-779).