Antimicrobial activity of succinylated quercetin’s derivatives additionally modified by amino acids

Abstract

Introduction/. Quercetin is one of the most famous flavonoids. Possibilities of chemical synthesis encourage the development and production of quercetin derivatives with new properties. Attempts to enhance the medicinal properties of quercetin by its chemical modifications are promising. The aim of the work is to study the antimicrobial properties of succylated quercetin derivatives extracted from plant raw materials, additionally modified with amino acids. Materials and methods. The antimicrobial activity of modified quercetin derivatives extracted from cultivated grapes, raspberry wood, cherry wood, wood and black currant leaves was determined. Samples with a quercetin content of 2.0% in the dry residue, which was modified with 2.0% of amber anhydride and 2.0% of the amino acids lysine and arginine, were studied. Substances of comparison were 2.0% extracts of unmodified natural quercetin extracted from the relevant parts of these plants. Studies of antimicrobial activity of substances were performed on 36 museum and clinical strains of microorganisms. Bacteriological studies were performed by the standard method of double serial dilutions. The minimum inhibitory concentration (MIC) was set at the lowest concentration of test substance that inhibited visible culture growth. The minimum bactericidal concentration (MBCC) was considered to be the lowest concentration that caused the death of at least 99.9% of bacteria. Results & discussion.  Succylated quercetin derivatives of grapevine, additionally modified with the amino acids lysine and arginine, showed high inhibitory activity against B. subtilis ATCC 6633 and 72.73% of S. aureus strains (MIC 15.6 μg / ml), E. coli strains and moderate bacteriostatic activity against the rest of the studied members of the family Enterobacteriaceae, P. aeruginosa, E. faecalis, members of the genus Streptococcus and coagulase-negative staphylococci. Modified quercetin derivatives of cherry wood showed high in vitro activity against B. subtilis ATCC 6633 and 72.73% of S. aureus strains (MIC in the range of 7.8–15.6 μg / ml), 50.0% of P. aeruginosa strains and 66.67% of the studied E. coli strains. Succillated quercetin derivatives of raspberry wood, additionally modified with the amino acids lysine and arginine, showed a high inhibitory effect on B. subtilis ATCC 6633, S. pneumoniae ATCC 49619 and 72.73% of S. aureus strains (MIC in the range of 7.8–15 μg / ml), 66.67% of E. coli strains (MIC 15.6 μg / ml). High bacteriostatic activity of succillated quercetin derivatives of raspberry wood was shown with additional modification by arginine in relation to 100.0% and lysine in relation to 50.0% of P. aeruginosa strains.

High inhibitory activity of succillated quercetin derivatives of black currant wood, additionally modified with amino acids, was shown in relation to 75.0% of P. aeruginosa strains (MIC 15.6 μg / ml), B. subtilis ATCC 6633 and 63.64% S. aureus strains ( MIC in the range of 7.8–15.6 μg / ml). High bactericidal action was carried out by succillated quercetin derivative of black currant wood, additionally modified with arginine, in relation to 27.27% of the studied strains of S. aureus (MBCC 15.6 μg / ml). For all studied members of the family Enterobacteriaceae for modified quercetin derivatives of black currant wood moderate bacteriostatic, and for E. coli and P. vulgaris also moderate bactericidal effect. Succulated quercetin derivatives from black currant leaves, additionally modified with amino acids, showed high bacteriostatic activity against B. subtilis ATCC 6633 and 81.82% of S. aureus strains, high bactericidal activity against 45.45% of S. aureus strains. For coagulose-negative staphylococci, their antimicrobial activity was mostly moderate. High bacteriostatic effect (MIC of 15.6 μg / ml) on the studied strains of P. aeruginosa and E. coli was more often observed with additional modification of succinate quercetin derivatives from currant leaves with the black amino acid arginine (75.0% of P. aeruginosa strains and 100.0% strains of E. coli strains) than lysine (25.0% of P. aeruginosa strains and 66.67% of E. coli strains). Conclusion. Significant and moderate bacteriostatic activity of modified quercetin derivatives extracted from plant raw materials in relation to the studied 36 strains of gram-positive and gram-negative microorganisms was found. Succilated quercetin derivatives, additionally modified with amino acids, showed high bacteriostatic activity against B. subtilis ATCC 6633, the vast majority of S. aureus, P. aeruginosa and E. coli strains (MIC in the range of 7.8–15.6 μg / ml). With regard to cogulase-negative staphylococci, E. faecalis and Streptococcus spp., as well as representatives of the genera Proteus, Klebsiella and Enterobacter, the degree of bacteriostatic action of the studied modified derivatives of quercetin extracted from plant raw materials was moderate (MIC in the range of 31.25 μg / ml. The expediency and prospects of searching for new original antimicrobial drugs based on succylated quercetin derivatives, additionally modified with the amino acids lysine and arginine, have been proved and experimentally substantiated.

Keywords:  succilated quercetin derivatives, amino acids, antimicrobial activity

DOI: 10.5281/zenodo.6634842