Molecular parameters and the antimicrobial activity of some n-substituted amino acids

Abstract

The concept of “drug likeness” is used when developing drugs for a potential biologically active substance, which must meet some specific criteria, in particular it should be bioavailable. The traditional method of “drug likeness” assessment is verification of compliance with Lipinski’s rule.
Aim. To determine the compliance of the “drug likeness” concept for some N-substituted amino acids and identify the quantitative “structure – microbiological activity” relationships.
Materials and methods. Using ChemOffice 2016 software the physicochemical parameters determining the bioavailability of some N-substituted amino acids were calculated. Determination of the possible correlations and quantitative ratios of the biological activity data experimentally obtained with the molar refraction (MR) values calculated was conducted using STATISTIKA 8 program.
Results and discussion. All compounds studied in their physicochemical properties meet the requirements for new BAS at the stage of testing their biological activity (correspond to Lipinski’s rule). The dependence of the microbiological action of some N-substituted amino acids on MR is maximal for compounds, which MR value is in the range of 2.13-4.53. The growth of all microorganisms was observed for unsubstituted amino acids (MR < 2.8). The maximum activity of all compounds studied was observed against gram-positive (B. subtilis and S. aureus), and the less activity was against gram-negative microorganisms (E. coli, P. vulgaris, P. aeruginosa) and fungi (C. albicans). It may be associated with the structural peculiarities of the cellular wall. The MR values calculated correlate satisfactorily with the experimental data of the antimicrobial activity of compounds.
Conclusions. Statistically significant values of MR correlation with the values of the antimicrobial activity of some N-substituted amino acids against the microorganisms studied have been determined. It quantitatively confirms the presence of the “structure – activity” relationship in this series of compounds.