Results of primary microbiological screening of modified quercetin derivatives

Introduction. The development of new effective and low-toxic drugs based on herbal raw materials is an urgent task of modern science. Quercetin is one of the most well-known and well-studied flavonoids. Attempts to enhance the medicinal properties of quercetin by its chemical modifications are promising. The aim of the work is to search for modified quercetin derivatives with high antimicrobial properties by their primary microbiological screening. Materials & methods. Primary microbiological screening of antimicrobial activity of 315 quercetin derivatives extracted from different plants was performed. Quercetin for research was obtained by acid hydrolysis of rutin. Determination of quercetin content in the extracts was performed using thin layer chromatography. For the primary screening standard test cultures of gram-positive and gram-negative bacteria were used that belonged to different taxonomic groups: Staphylococcus aureus ATCC 25923, Esсherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Bacillus subtilis ATCC6633, Proteus vulgaris ATCC 4636. Antifungal activity of the compounds was studied for the reference strain of Candida albicans ATCC 885-653. Determination of antimicrobial and anticandidal activity of the new compounds was carried out with the help of the diffusion method of "wells" with the measurement of the diameters of the zones of growth retardation of microorganisms. Results & discussion. In the study of antimicrobial activity of natural quercetin of all plants in the studied concentrations found its moderate effect on test strains of S. aureus ATCC 25923, B. subtilis ATCC 6633, E. coli ATCC 25922 and C. albicans ATCC 653-885. Moderate antimicrobial activity of the vast majority of formalized and succylated modifications of quercetin extracted from all studied plants against all reference strains of microorganisms was found. With additional modification of formalized and succyllated samples of amber apricot quercetin with amino acids, the sensitivity of test strains of gram-negative microorganisms and C. albicans ATCC 653/885 did not change significantly and remained moderate. S. aureus ATCC 25923 showed high sensitivity to 62.5% of succillated and 25.0% of formalized apricot quercetin derivatives, further modified with amino acids. S. aureus ATCC 25923 showed high activity against all 100.0% of succylated and 62.5% of formalized quercetin derivatives from grapevine, additionally modified with amino acids. 95.0% of the samples showed high activity against the test strain of B. subtilis ATCC 6633, in particular 75.0% of formalized and all succylated derivatives, further modified with amino acids. S. aureus ATCC 25923 showed high activity against 50.0% of succylated and 25.0% formalized quercetin derivatives from grape leaves, additionally modified with amino acids, B. subtilis ATCC 6633 - against 62.5% of formalized and all succylated derivatives from grapevine. For 37.5% of succylated modifications of quercetin from leaves and 50.0% of succylated modifications of quercetin from grapes, additionally modified with amino acids, a high antimicrobial effect against the gram-negative test strain of E. coli ATCC 25922 was proved. High sensitivity of S. aureus ATCC 25923 was found for 85.0% of quercetin samples from raspberry wood and 65.0% of quercetin samples from raspberry leaves, additionally modified with amino acids, B. subtilis ATCC 6633 - respectively 90.0% and 95.0 % of samples. 37.5% of succyllated quercetin derivatives from raspberry leaves, additionally modified with amino acids, were highly active against the test strain of E. coli ATCC 25922. The most active against gram-positive and gram-negative microorganisms were formalized and succylated derivatives of quercetin from the leaves and wood of black currant, additionally modified with lysine and arginine. All 100.0% of quercetin derivatives, additionally modified with amino acids, showed high antimicrobial activity against the reference strain of S. aureus ATCC 25923 and more than 95.0% - against the test strain of B. subtilis ATCC 6633. The test strain of E. coli ATCC 25922 showed high sensitivity up to 45.0%, P. vulgaris ATCC 4636 - up to 10.0% and P.aeruginosa ATCC 27853 - up to 20.0% of quercetin derivatives from black currant leaves, additionally modified with amino acids. High antimicrobial activity against gram-negative microorganisms was most often shown by succylated modifications of quercetin, additionally modified with amino acids. A quarter of the succylated quercetin derivatives from black currant wood, additionally modified with amino acids, showed high antimicrobial activity against E. coli ATCC 25922 and half - against the test strain P.aeruginosa ATCC 27853. 75.0% of samples of succyllated quercetin from black currant leaves, additionally modified with amino acids, against E. coli ATCC 25922, 25.0% - against P. vulgaris ATCC 4636 and 50.0%. - to P.aeruginosa ATCC 27853 were highly active. S. aureus ATCC 25923 showed high sensitivity to 83.3% of formalized and 87.5% of succyllates, B. subtilis ATCC 6633 - respectively to 75.0% and 100.0% of quercetin derivatives from cherry leaves, additionally modified with amino acids. Among gram-negative microorganisms, the test strain of E. coli ATCC 25922 showed high sensitivity to 37.5% of samples of formalized and up to 100.0% of succyllated varieties of cherry wood quercetin, additionally modified with amino acids. More than a third of the investigated succylated modifications of cherry quercetin, additionally modified with amino acids, were highly active against the test strain of P.aeruginosa ATCC 27853. Additional modification of formalized and succylated derivatives of cherry quercetin with conventional amino acids did not significantly affect the sensitivity of P. vulgaris ATCC 4636 and C. albicans ATCC 653-885, which remained moderate. Conclusion. 1. The results of primary microbiological screening of 315 samples of quercetin and its modified derivatives showed mostly moderate sensitivity of the tested test strains of gram-positive, gram-negative microorganisms and test strain C. albicans ATCC 653-885 to unmodified concentrated, formalized and succylated quercetin of various concentrations. 2. Varieties of modified quercetin, additionally modified with the amino acids lysine and arginine, were the most active in terms of antimicrobial action. 3. The vast majority of the studied extracts of quercetin, further modified with amino acids, showed high antimicrobial activity against test strains of gram-positive microorganisms 4. With regard to gram-negative microorganisms, the most active were succulent extracts of quercetin, modified with amino acids, extracted from the leaves and vines of grapes, raspberry wood, cherry wood, wood and black currant leaves. 5. Moderate anticandidal activity of all investigated samples of quercetin and its modified derivatives was established. 6. The results of the study prove the prospects and feasibility of further in-depth study of the spectrum and degree of antimicrobial activity of selected substances in order to develop new antimicrobial agents based on them