The Application of CA and PCA to the Evaluation of Lipophilicity and Physicochemical Properties of Tetracyclic Diazaphenothiazine Derivatives

Anna Nycz-Empel; Katarzyna Bober; Mirosław Wyszomirski; Ewa Kisiel; Andrzej Zięba

doi:10.1155/2019/8131235

The Application of CA and PCA to the Evaluation of Lipophilicity and Physicochemical Properties of Tetracyclic Diazaphenothiazine Derivatives

J Anal Methods Chem. 2019 Oct 20:2019:8131235. doi: 10.1155/2019/8131235. eCollection 2019.

Authors

Anna Nycz-Empel¹, Katarzyna Bober², Mirosław Wyszomirski³, Ewa Kisiel¹, Andrzej Zięba¹

Affiliations

¹ Department of Organic Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Jagiellonska 4, 41-200 Sosnowiec, Poland.
² Deparment of Analytical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Jagiellonska 4, 41-200 Sosnowiec, Poland.
³ University of Bielsko-Biala, Faculty of Materials, Civil and Environmental Engineering, Willowa 2, 43-309 Bielsko-Biala, Poland.

Abstract

The subject of the study was 11 new synthetized tetracyclic diazaphenothiazine derivatives. Using thin-layer chromatography in a reverse phase system (RP-TLC), their R _M0 lipophilicity parameter was determined. The mobile phase was composed of 0.2 M Tris buffer (pH = 7.4) and acetone (POCH S.A., Gliwice, Poland) in different concentrations. Using computer programs, based on different computational algorithms, theoretical values of lipophilicity (AClogP, ALOGP, ALOGPs, miLogP, MLOGP, XLOGP2, and XLOGP3) as well as molecular descriptors (molecular weight, volume of a molecule, dipole moment, polar surface, and energy of HOMO orbitals and LUMO orbitals) and parameters of biological activity: human intestinal absorption (HIA), plasma protein binding (PPB), and blood-brain barrier (BBB), were determined. The correlations between the experimental values of lipophilicity and theoretically calculated lipophilic values and also between experimental values of lipophilicity and values of physicochemical or biological properties were assessed. A certain relationship between structure and lipophilicity was found. On the other hand, the relationships between R _M0 and physicochemical or biological properties were not statistically significant and therefore unusable. For all analysed values, an analysis of similarities and principal component analyses were also made. The obtained dendrograms for the analysis of lipophilicity and physicochemical and biological properties indicate the relationship between experimental values of lipophilicity and structure in the case of theoretical lipophilicity values only. PCA, on the other hand, showed that ALOGP, MLOGP, miLogP, and BBB and molar volume have the largest share in the description of the entire system. Distribution of compounds on the area of factors also indicates the connections between them related to their structure.