Assessment of Lipophilicity Parameters of Antimicrobial and Immunosuppressive Compounds

• Published in: Molecules (Basel, Switzerland) Vol. 28; no. 6; p. 2820
• Main Authors: Wardecki, Dawid, Dołowy, Małgorzata, Bober-Majnusz, Katarzyna
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.03.2023; MDPI
• Subjects: Acetonitrile; Algorithms; Analysis; Anti-Infective Agents - pharmacology; Antibiotics; Antimicrobial agents; antimicrobial drugs; bioactive molecules; Biological activity; Chromatography; Chromatography, Reverse-Phase - methods; Chromatography, Thin Layer - methods; Drugs; Experimental methods; FDA approval; Gram-negative bacteria; Hydrophobic and Hydrophilic Interactions; Immunosuppressive agents; Immunosuppressive Agents - pharmacology; immunosuppressive compounds; Inhibitor drugs; Kinases; lipophilicity; Physiological aspects; Pneumonia; Rankings; Reproducibility; Research methodology; Signal transduction; Software; Solubility; Streptococcus infections; TLC; Poland; lipophilicity; TLC; immunosuppressive compounds; antimicrobial drugs; bioactive molecules; chromatography
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules28062820

Lipophilicity in addition to the solubility, acid-base character and stability is one of the most important physicochemical parameters of a compound required to assess the ADMET properties (absorption, distribution, metabolism, excretion and toxicity) of a bioactive molecule. Therefore, the subject of this work was to determine the lipophilicity parameters of selected antimicrobial and immunosuppressive compounds such as delafloxacin, linezolid, sutezolid, ceftazidime, everolimus and zotarolimus using thin-layer chromatography in reversed phase system (RP-TLC). The chromatographic parameters of lipophilicity (RMW) for tested compounds were determined on different stationary phases: RP18F254, RP18WF254 and RP2F254 using ethanol, acetonitrile, and propan-2-ol as organic modifiers of mobile phases used. Chromatographically established RMW values were compared with partition coefficients obtained by different computational methods (AlogPs, AClogP, AlogP, MlogP, XlogP2, XlogP3, logPKOWWIN, ACD/logP, milogP). Both cluster and principal component analysis (CA and PCA) of the received results allowed us to compare the lipophilic nature of the studied compounds. The sum of ranking differences analysis (SRD) of all lipophilicity parameters was helpful to select the most effective method of determining the lipophilicity of the investigated compounds. The presented results demonstrate that RP-TLC method may be a good tool in determining the lipophilic properties of studied substances. Obtained lipophilic parameters of the compounds can be valuable in the design of their new derivatives as efficient antimicrobial and immunosuppressive agents.