Determination of ligand efficiency indices in a group of 7H-purine-2,6-dione derivatives with psychotropic activity using micellar electrokinetic chromatography.

Discovering hit compounds and optimization processes in medicinal chemistry nowadays could be improved by predictive tools, based on the relationship between structure of molecules and lipophilic properties. Lipophilicity of drug candidate can affect both the pharmacokinetic and pharmacodynamics properties, in particular, the ability of a molecule to cross the cell membrane. Among the new methods for determination of the lipophilicity of compounds, micellar electrokinetic chromatography (MEKC) is considered to be an appropriate one for bioactive molecules, as it closely mimics the physiological conditions. In this paper MEKC was used for the estimation of the lipophilicity of 24 derivatives of 8-alkoxy-7H-purine-2,6-dione, designed and synthesized as potential antidepressant/anxiolytic and antipsychotic agents. The results of experimental method were compared with calculated in silico parameters (AlogPs and milogP by Virtual Computational Laboratory website, log P _Pallas by Pallas 3.1, Mlog P by Marvin, log P _ChemS by ChemSketch, log P _ChemDraw by ChemBioUltra) using Principal Component Analysis (PCA) method. Finally, using estimated log P values for selected compounds ligand - lipophilicity efficiency (LLE), per cent efficiency index (PEI), and binding efficiency index (BEI) parameters were calculated. Applied MEKC procedure could be used for selection of potential lead structure in a group of 7H-purine-2,6-dione derivatives.
(© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)