Investigation of Hydro-Lipophilic Properties of N-Alkoxyphenylhydroxynaphthalenecarboxamides †.

Iva Kapustikova,Violetta Kozik,Andrzej Bak,Tomas Gonec,Josef Jampilek,Jiri Kos

doi:10.3390/molecules23071635

Iva Kapustikova, Violetta Kozik + Show 4 more

Open Access

https://doi.org/10.3390/molecules23071635

Copy DOI

Journal: Molecules (Basel, Switzerland)	Publication Date: Jul 4, 2018
Citations: 11	License type: CC BY 4.0

Affiliation: University of Silesia

Abstract

The evaluation of the lipophilic characteristics of biologically active agents is indispensable for the rational design of ADMET-tailored structure–activity models. N-Alkoxy-3-hydroxynaphthalene-2-carboxanilides, N-alkoxy-1-hydroxynaphthalene-2-carboxanilides, and N-alkoxy-2-hydroxynaphthalene-1-carboxanilides were recently reported as a series of compounds with antimycobacterial, antibacterial, and herbicidal activity. As it was found that the lipophilicity of these biologically active agents determines their activity, the hydro-lipophilic properties of all three series were investigated in this study. All 57 anilides were analyzed using the reversed-phase high-performance liquid chromatography method for the measurement of lipophilicity. The procedure was performed under isocratic conditions with methanol as an organic modifier in the mobile phase using an end-capped non-polar C18 stationary reversed-phase column. In the present study, a range of software lipophilicity predictors for the estimation of clogP values of a set of N-alkoxyphenylhydroxynaphthalenecarboxamides was employed and subsequently cross-compared with experimental parameters. Thus, the empirical values of lipophilicity (logk) and the distributive parameters (π) were compared with the corresponding in silico characteristics that were calculated using alternative methods for deducing the lipophilic features. To scrutinize (dis)similarities between the derivatives, a PCA procedure was applied to visualize the major differences in the performance of molecules with respect to their lipophilic profile, molecular weight, and violations of Lipinski’s Rule of Five.

Highlights

The assessment of a molecular property profile that is crucial for the bioavailability of compounds and critical for the prospective drug candidate is possible by an a priori calculation of molecular descriptors
To scrutinizesimilarities between the derivatives, a Principal component (PCA) procedure was applied to visualize the major differences in the performance of molecules with respect to their lipophilic profile, molecular weight, and violations of Lipinski’s Rule of Five
A of N-substituted 3-hydroxynaphthalene-2-carboxanilides 1a–19a in yields ranging from 52% to

Summary

Introduction

The assessment of a molecular property profile that is crucial for the bioavailability of compounds and critical for the prospective drug candidate is possible by an a priori calculation of molecular descriptors. Molecular descriptors quantifying drug-like properties are calculated based on the molecular formula; the reliability of the resulting values of such properties is still questionable. ‘sieve’) that relates the calculable physicochemical properties to the complex in vivo pharmacokinetic parameter that comprises aqueous solubility and oral bioavailability. Lipophilicity is known as a first-rate physicochemical parameter that is increasingly important in the description of both pharmacokinetic (ADMET) and pharmacodynamic aspects of drug–receptor/enzyme interactions, which often correlate well with the bioactivity of chemicals [4,5,6]

Objectives

Results

Conclusion