Chromatographic parameters as tools for predicting the biological activity of azo derivatives

Preliminary assessment of the bioactive profile of azo derivatives was performed applying drug-likeness rules. As the presumed criteria of lipophilicity chromatographic parameters (RM0, m and C0) were calculated in mixtures water/ methanol and water/ acetonitrile by using reversed phase thin-layer chromatography (RPTLC C18/ UV254s). The relationships between chromatographic parameters and relevant software parameters of biological activity of azo derivatives were examined by linear regression and by two multivariate methods. Good linear relationships for each applied system were obtained. The multivariate methods show similarity of the chromatographic parameters (RM0, C0) with standard measure of lipophilicity and pharmacokinetic predictors. The chromatographic parameter m obtained in the same conditions exhibits better agreement with the drug-likeness and toxicity parameters. On the values of azo derivatives’ bioactivity parameters the polarity of the substituent has higher impact than its electronic effects.

Comparison of the Utility of RP-TLC Technique and Different Computational Methods to Assess the Lipophilicity of Selected Antiparasitic, Antihypertensive, and Anti-inflammatory Drugs

The aim of this study was to assess the lipophilicity of selected antiparasitic, antihypertensive and non-steroidal anti-inflammatory drugs (NSAIDs) by means of reversed phase–thin layer chromatography (RP-TLC) as well by using Soczewiński–Wachtmeister’s and J. Ościk’s equations. The lipophilicity parameters of all examined compounds obtained under various chromatographic systems (i.e., methanol-water and acetone-water, respectively) and those determined on the basis of Soczewiński-Wachtmeister’s and Ościk’s equations (i.e., RMWS and RMWO) were compared with the theoretical ones (e.g., AlogPs, AClogP, milogP, AlogP, MlogP, XlogP2, XlogP3) and the experimental value of the partition coefficient (logPexp). It was found that the RMWS parameter may be a good alternative tool in describing the lipophilic nature of biologically active compounds with a high and low lipophilicity (i.e., antihypertensive and antiparasitic drugs). Meanwhile, the RMWO was more suitable for compounds with a medium lipophilicity (i.e., non-steroidal anti-inflammatory drugs). The chromatographic parameter 0(a) can be helpful for the prediction of partition coefficients, i.e., AClogP, XlogP3, as well as logPexp of examined compounds.

A contribution to the study of hydrophobicity (lipophilicity) of bile acids with an emphasis on oxo derivatives of 5β-cholanoic acid

Due to their promotory action on the transport of some drugs through various membranes (lipophilic barriers), oxo derivatives of bile acids have recently been increasingly used in biopharmacy. These compounds exhibit also a lower membranolytic (toxic) activity than their hydroxy analogues. Because of that it is of special importance to find out the descriptors that would adequately describe the structure of bile acids and their biological activity and be used to model the quantitative structure-activity relationship. In view of this, the present work is concerned with the application of the chromatographic parameter RM0 obtained by normal-phase thin-layer chromatography in the solvent system toluene-butanol and silica gel as stationary phase to describe the lipophilicity of bile acids. Also, the work introduces a new molecular descriptor (ND) that reflects both 2D and 3D topological characteristics of the molecule. Between the retention constant, RM0 and the descriptor ND there is a good correlation, and both RM0, and ND describe sufficiently well the structural (conformational) changes that arise in the process of oxidation of the OH group of the steroid skeleton to an oxo group. On the other hand, the in silico descriptors of lipophilicity, logP (atomic-based prediction) and ClogP (fragment-based prediction) predict the hydrophobicity of bile acid oxo derivatives with a certain error.

Quantitative Relationships Between Structure, Aggregation Properties and Antimicrobial Activity of Quaternary Ammonium Bolaamphiphiles

QSAR analysis employing Kubinyi's bilinear model was applied to examine the relationship between the structure (characterized by the lengths of the terminal hydrocarbon chain, m, and of the hydrocarbon spacer chain, y), lipophilicity (characterized by the chromatographic parameter Rm and aggregation properties expressed through the critical micellar concentration cK), and antimicrobial activity (characterized by the minimum inhibition concentration, MIC) of quaternary ammonium bolaamphiphiles. The log cK = f(m) dependence was found to be linear whereas the log (1/MIC) = f(m), log (1/MIC) = f(y), log (1/MIC) = f (log cK) and log (1/MIC) = f(Rm) dependences were nonlinear. The effect of the hydrophobic terminal chains (m) and of the hydrophobic spacer chain (y) on the aggregation properties and on the biological activity of the substances was studied.