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

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 RM0 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 RM0 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.

Easy-To-Access Quinolone Derivatives Exhibiting Antibacterial and Anti-Parasitic Activities

“…Although it has been observed that Clog P values generated from different computer programs differ from the experimentally determine log P , often with a difference of more than 0.5 units; there however exist a strong correlation (r > 0.6) between computer generated Clog P values and experimentally determine log P . This evidence makes Clog P values a usable guide in early hit finding [ 60 ]. Herein, we generated Clog P values using ACD/Chemsketch freeware version 12.0.…”

“…Trypanosoma brucei brucei 427 trypomastigotes were cultured in iscove’s modified Dulbecco’s medium (IMDM; Lonza, Basel, Switzerland) supplemented with 10% fetal calf serum, HMI-9 supplement [ 68 ], hypoxanthine and penicillin/streptomycin at 37 °C in a 5% CO 2 incubator. Serial dilutions of test compounds were incubated with the parasites in 96-well plates for 24 h and residual parasite viability in the wells determined as previously reported [ 60 ].…”

Towards Anticancer and Antibacterial Agents: Design and Synthesis of 1,2,3-Triazol-quinobenzothiazine Derivatives

“…In practice, reaction products with a 1,2,3-triazole group in position 4 of the phenothiazine system (see Figure 1B) were synthesized and characterized [27]. The details of the preparation of quinobenzothiazinium derivatives that revealed their noteworthy biological properties were presented in our previous reports [28][29][30]. The direction and strength of the antibacterial and anticancer activity depended on the presence and nature of the substituents in the tetracyclic quinobenzothiazinium system.…”

Microbial Synthesis and Evaluation of Fungistatic Activity of 3-Butyl-3-hydroxyphthalide, the Mammalian Metabolite of 3-n-Butylidenephthalide

“…Lipophilicity, defined as the affinity of a compound towards nonpolar phase, is also significant for potential drug evaluation [ 29 ]. The log P parameter is linked to the absorption, distribution, metabolism and excretion processes [ 30 , 31 ].…”