STUDY OF ANTISTAPHYLOCOCCAL POTENTIAL OF NEWLY SYNTHESIZED ARYL ACYCLIC AMINO ALCOHOL DERIVATIVES
doi.org/10.17721/1728.2748.2025.100.72-80
Keywords:
MRSA, MSSA, antibiotic resistance, mecA gene, cefoxitin, amino alcohols, MICAbstract
Background. Staphylococci remain priority pathogens among infectious agents. The growing antibiotic resistance of this species poses a serious threat to modern medicine. The limited number of effective antibiotics makes it difficult to treat staphylococcal infections and exacerbates their negative consequences for patients. Particular attention should be paid to Staphylococcus aureus’s resistance to methicillin, a “typical” phenomenon among hospital infections. Therefore, searching for new approaches to combat this pathogen is extremely important.
Methods. The object of the study was 10 compounds of aryl acyclic amino alcohol derivatives and 50 strains of Staphylococcus aureus. The antistaphylococcal properties were determined by the disk diffusion method and the serial dilution. MRSA was identified by the phenotypic method using cefoxitin disks. The effectiveness of the compounds was determined by comparing the susceptibility of MRSA and MSSA.
Results. Among the 50 strains, 24 were identified as containing the mecA gene by phenotypic features. The results of antibiotic susceptibility testing demonstrated predominant resistance to benzylpenicillin drugs. Following breakpoints of antibiotic resistance, resistance to benzylpenicillin was 74%. Sensitivity to tetracycline was found in 54% of strains, and to vancomycin - in 84%. The studied substances showed high efficiency against staphylococci. The activity of compounds Kc1, Kp18, Kp19 was on par with vancomycin, and the MIC for most isolates did not exceed 1 μg/ml. The inhibitory effect of the compounds was observed in the concentration range of 0.98-1.95 μg/ml. MSSA strains showed a slightly higher sensitivity, which may indicate the potential specificity of the compounds to PBP.
Conclusions. The antimicrobial properties of aryl acyclic amino alcohol derivatives as potential antistaphylococcal agents were investigated. The effectiveness of the drugs in comparison with commercial drugs and between the groups of MSSA and MRSA was determined. A group of compounds with the most pronounced activity against S. aureus isolates, including MRSA, was identified.
References
Baker, J. R., Cossar, P. J., Blaskovich, M. A. T., Elliott, A. G., Zuegg, J., Cooper, M. A., Lewis, P. J., & McCluskey, A. (2022). Amino Alcohols as Potential Antibiotic and Antifungal Leads. Molecules, 27(7), 2050. https://doi.org/10.3390/molecules27072050
DeLeo, F. R., & Chambers, H. F. (2009). Reemergence of antibiotic-resistant Staphylococcus aureus in the genomics era. Journal of Clinical Investigation, 119(9), 2464–2474. https://doi.org/10.1172/JCI38226
Hiramatsu, K., Cui, L., Kuroda, M., & Ito, T. (2001). The emergence and evolution of methicillin-resistant Staphylococcus aureus. Trends in Microbiology, 9(10), 486–493. https://doi.org/10.1016/S0966-842X(01)02175-8
Klevens, R. M., A. Morrison, M., & Nadle, J. (2007). Invasive Methicillin-Resistant Staphylococcus aureus Infections in the United States. JAMA, 298(15), 1763–1771. https://doi.org/10.1001/jama.298.15.1763
Kowalska-Krochmal, B., & Dudek-Wicher, R. (2021). pathogens The Minimum Inhibitory Concentration of Antibiotics: Methods, Interpretation, Clinical Relevance. https://doi.org/10.3390/pathogens10020165
Lakhundi, S., & Zhang, K. (2018). Methicillin-Resistant Staphylococcus aureus: Molecular Characterization, Evolution, and Epidemiology. Clinical Microbiology Reviews, 31(4). https://doi.org/10.1128/CMR.00020-18
Osypchuk, N., Nastenko, V. B., Shirobokov, V. P., & Korotkyi, Y. V. (2020). Sensitivity of antifungal preparations of Сandida isolates from sub-biotopes of the human oral cavity. Regulatory Mechanisms in Biosystems, 11(1), 82–87. https://doi.org/10.15421/022011
Otto, M. (2018). Staphylococcal Biofilms. Microbiology Spectrum, 6(4). https://doi.org/10.1128/microbiolspec.GPP3-0023-2018
Skov, R., Varga, A., Matuschek, E., Åhman, J., Bemis, D., Bengtsson, B., Sunde, M., Humphries, R., Westblade, L., Guardabassi, L., & Kahlmeter, G. (2020). EUCAST disc diffusion criteria for the detection of mecA-Mediated β-lactam resistance in Staphylococcus pseudintermedius: oxacillin versus cefoxitin. Clinical Microbiology and Infection, 26(1), 122.e1-122.e6. https://doi.org/10.1016/j.cmi.2019.05.002
Tacconelli, E., Carrara, E., Savoldi, A., Harbarth, S., Mendelson, M., Monnet, D. L., Pulcini, C., Kahlmeter, G., Kluytmans, J., Carmeli, Y., Ouellette, M., Outterson, K., Patel, J., Cavaleri, M., Cox, E. M., Houchens, C. R., Grayson, M. L., Hansen, P., Singh, N., … Zorzet, A. (2018). Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. The Lancet Infectious Diseases, 18(3), 318–327. https://doi.org/10.1016/S1473-3099(17)30753-3
The European Committee on Antimicrobial Susceptibility Testing. (2024). Breakpoint tables for interpretation of MICs and zone diameters (Version 14.0). http://www.eucast.org
Tong, S. Y. C., Davis, J. S., Eichenberger, E., Holland, T. L., & Fowler, V. G. (2015). Staphylococcus aureus Infections: Epidemiology, Pathophysiology, Clinical Manifestations, and Management. Clinical Microbiology Reviews, 28(3), 603–661. https://doi.org/10.1128/CMR.00134-14
WHO. (2017). Prioritization Of Pathogens To Guide Discovery, Research And Development Of New Antibiotics For Drug-Resistant Bacterial Infections, Including Tuberculosis. file:///C:/Users/User/Downloads/WHO-EMP-IAU-2017.12-eng.pdf
WHO. (2024). WHO Bacterial Priority Pathogens List, 2024: bacterial pathogens of public health importance to guide research, development and strategies to prevent and control antimicrobial resistance. 1–56. https://iris.who.int/bitstream/handle/10665/376776/9789240093461-eng.pdf?sequence=1
Zwittink, R. D., Wielders, C. C., Notermans, D. W., Verkaik, N. J., Schoffelen, A. F., Witteveen, S., Ganesh, V. A., de Haan, A., Bos, J., Bakker, J., Schneeberger-van der Linden, C., Kuijper, E. J., de Greeff, S. C., & Hendrickx, A. P. (2022). Multidrug-resistant organisms in patients from Ukraine in the Netherlands, March to August 2022. Eurosurveillance, 27(50), 1–8. https://doi.org/10.2807/1560-7917.ES.2022.27.50.2200896
Березняков І. (2020). Стан антибіотикорезистентності в Україні: результати дослідження АУРА. Здоров’я України, 5, 21–23. https://healthua.com/multimedia/userfiles/files/2020/Hirurg_5_2020/Hirurg_5_2020_20-23.pdf
Дронова, М. Л. (2016). Фармакодинамічні особливості антибактеріальної дії нових похідних арилаліфатичних аміноспиртів http://dspace.nuph.edu.ua/handle/123456789/11091
Настенко, В. Б. (2022). Дослідження антистафілококової активності новосинтезованих похідних четвертинних солей арил ациклічних аміноспиртів щодо клінічних штамів Staphyloсoссus aureus. У О. Г. Алексєєв, С. Д. Шаповал, І. М. Фуштей (Ред.), Матеріали ХVI Всеукраїнської науково-практичної конференції молодих вчених «Актуальні питання клінічної медицини» (с. 277). Державний заклад «Запорізька медична академія післядипломної освіти Міністерства охорони здоров’я України».
