Antimicrobial Activity of New <i>N</i>-substituted Amides of Aroylpyruvic Acids and Their Silver Salts

Abstract

Introduction. An important direction of modern pharmacy is the production of new domestic substances with anti-infectious activity, within the framework of ensuring the technological sovereignty of the state. Optimization of methods for determining antimicrobial activity is an integral part of these studies. Previously obtained silver salts of pyrazoles and pyrazolecarboxamideshad high antimicrobial activity. This work presents the results of determining the antimicrobial activity of new biologically active compounds synthesized by a salt formation reaction with silver ions at the carboxyl group of aroylpyruvic acid amides containing anthranilic acid in the amide fragment.Aim. Obtaining previously unknown amides of aroylpyruvic acids and their silver salts and studying their antimicrobial activity (AMA).Materials and methods. New N-substituted amides of anthranilic acids and their silver salts were obtained by organic synthesis methods. To study their antimicrobial activity, a micromethod of double serial dilutions was used on screening strains of S. aureus ATCC 6538P, E. coli ATCC 25922, as well as E. faecalis ATCC 29212, S. aureus Wood 46, S. abony No. 103/39 for highly active compounds. Additionally, a method of accounting for the results was carried out using the phenomenon of fluorescence in interaction with rezazurin, indicating the presence of living microbial cells.Results and discussion. The presence of antibacterial activity of silver salts 2a and 2b in relation to the studied strains was established: the minimum suppressive concentration (MPC) of compound 2a is 23.4–31.2 micrograms/ml, 2b is 3.9–5.8 micrograms/ml. When taking into account the results of the study of AMA using the phenomenon of fluorescence, it was found that they either coincide with the values of MPC determined visually, or indicate less antibacterial activity. Comparison of these results and seeding of the contents of the wells on a dense nutrient medium with respect to screening strains indicates that the suppression of fluorescence in experimental wells in the range of 99–82 % compared with the control is accompanied by the absence of bacterial growth (bactericidal effect), with fluorescence inhibition of less than 60 %, a pronounced growth of microorganisms is observed. In the intermediate range, the growth of single colonies is observed (bacteriostatic effect).Conclusion. The results of the study showed that the new silver salts of N-substituted amides of aroylpyruvic acids have high antimicrobial activity. The correspondence of the type of antibacterial activity to the degree of fluorescence inhibition was established.

Keywords

• <i>n</i>-substituted amides of aroylpyruvic acids and their silver salts
• antimicrobial activity
• fluorescence