Chromatographic and computational screening of lipophilicity and pharmacokinetics of newly synthesized betulin-1,4-quinone hybrids

Abstract

Lipophilicity is one of the most important parameters determining the pharmacodynamic and pharmacokinetic properties, as well as the toxicity of many compounds. The subject of the research was to determine the lipophilicity of betulin-1,4-quinone hybrids using thin layer chro-matography in reverse phase system and computer programs to calculate its theoretical models. The correlation between the experimental and theoretical values of lipophilicity was analyzed. Lipinski’s and Veber’s rules, as well as penetration through the blood–brain barrier were also determined using computer programs. For all of the analyzed values, a similarity analysis was performed. The dendrograms for the experimental and theoretical lipophilicity show that there is a correlation between them. However, the dendrograms for the experimental lipophilicity and pharmacokinetic parameters indicate that there is no correlation between the structure and the pharmacological properties. Hybrids exhibit a high biological activity against cancer cell lines, with a high level of NAD[P]H-quinone oxidoreductase (NQO1) protein. The enzymatic assay used has shown that these compounds are good NQO1 substrates, as evidenced by the increasing metabolic rates relative to that of streptonigrin. The similarity analysis has also shown that there is no correlation between lipophilicity and biological activity for the tested compounds.