Prediction of overcoming the BBB by pharmacological compounds of various chemical natures using analysis of physicochemical properties in silico, in vitro with confirmation of calculated results by in vivo experiments

Background. To assess the effectiveness of drugs used to treat diseases, it is important to know the physicochemical properties of a substance, especially the ability of a substance to penetrate the cell membrane. There are many methods for determining the ability of substances to penetrate the BBB. The model of substance distribution between the membrane and extracellular fluid can be expressed by a numerical characteristic of the substance distribution (lipophilicity), called logP, which is calculated as the distribution of a substance between the organic phase and water. Aim. The aim is to determine and compare the values ​​of parameters that can act as predictors for overcoming the BBB in silico, in vitro and to verify the obtained data using the in vivo method. Materials and methods. To determine the predictors of overcoming the BBB, we used in silico methods - the Way2Drug portal and the VEGA ZZ program, in vitro using spectrophotometry in the UV region to determine the practical LogP and pharmacological analysis of the effect after intraperitoneal administration of substances using behavioral tests - open field, pole test, plus maze, sexual motivation, rotarod. Results. The values ​​​​of BBB overcoming predictors were determined for 6-GDA, oxytocin, kisspeptin-10 and haloperidol (DEEP, MEP, MLP, PSA, HBASS, HBDON, LogS, LogBB, LogP, etc.). The distribution coefficients of the studied substances were calculated based on optical density data (6GDA- -1.01; Kiss-10- -0.79; oxytocin- -0.816; haloperidol- -0.2). A pharmacological study of the penetration of substances through the BBB by effect was conducted. Comparison of theoretical (obtained in silico), experimental (UFS) values ​​of coefficients (LogP practical) with pharmacological analysis. As a result of all analyses, it was established that only haloperidol has properties that favor penetration through the BBB. Conclusion. It is shown that the results of physicochemical properties obtained in silico and in vitro for predicting the penetration of drugs through the BBB are confirmed by pharmacological analysis based on behavioral effects.