Estimation of the activity of modified pyrimidine nucleoside derivatives on bacteria cells
https://doi.org/10.29235/1029-8940-2023-68-1-55-63
Abstract
The increase in prevalence of antimicrobial-resistant bacteria (ARB) is currently a serious threat, thus there is a need for new classes antimicrobial compounds to combat infections caused by these ARB. The growth inhibition ability of derivatives of the components of nucleic acids has been well-characterized but not for its antimicrobial characteristics. It was found that modified nucleosides arabinofuranosylcytosine (cytarabine, ara-C), [1-(2′,3′,5′-tri-O-acetyl-β-D-ribofuranosyl)- 4-(1,2,4-triazol-1-yl)]uracil (TTU), and nucleotides cytarabine-5′-monophosphate (ara-CMP), and O2,2′-cyclocytidine-5′- monophosphate (cyclocytidine monophosphate, cyclo-CMP) were able to inhibit Escherichia coli, Sarcina lutea, Bacillus cereus, and Proteus mirabilis strains in a time and dose dependent manner via killing kinetics assay. It was demonstrated that studied modified pyrimidine nucleosides derivatives enhanced the production of intracellular reactive oxygen species (ROS) over time (validated via DCFA-DA probe assay). This study has revealed the mechanism of action of cytarabine, cyclocytidine monophosphate, and TTU as an antimicrobial agent for the first time, and has shown that these pyrimidine derivatives enhanced might be able to combat infections caused by E. coli, S. lutea, B. cereus, and P. mirabilis in the future.
About the Authors
A. ShihadBelarus
Arshed Shihad – Postgraduate student
23/1, Dolgobrodskaya Str., 220070, Minsk
A. G. Sysa
Belarus
Aliaksei G. Sysa – Ph. D. (Chem.), Associate Professor
23/1, Dolgobrodskaya Str., 220070, Minsk
References
1. Nathan C., Cars O. Antibiotic resistance-problems, progress, and prospects. New England Journal of Medicine, 2014, vol. 371, no. 19, рр. 1761–1763. https://doi.org/10.1056/NEJMp1408040
2. Nathan C. Antibiotics at the crossroads. Nature, 2004, vol. 431, no. 7011, рр. 899–902. https://doi.org/10.1038/431899a
3. Davies J., Davies D. Origins and evolution of antibiotic resistance. Microbiology and Molecular Biology Reviews, 2010, vol. 74, no. 3, рр. 417–433. https://doi.org/10.1128/MMBR.00016-10
4. van Boeckel T. P., Brower Ch., Gilbert M., Grenfell B. T., Levin S. A., Robinson T. P., Teillant A., Laxminarayan R. Global trends in antimicrobial use in food animals. Proceedings of the National Academy of Sciences, 2015, vol. 112, no. 18, рр. 5649–5654. https://doi.org/10.1073/pnas.1503141112
5. Roca I., Akova M., Baquero F., Carlet J., Cavaleri M., Coenen S. [et al]. The global threat of antimicrobial resistance: science for intervention. New Microbes and New Infections, 2015, vol. 6, pp. 22–29. https://doi.org/10.1016/j.nmni.2015.02.007
6. Rossolini G. M., Arena F., Pecile P., Pollini S. Update on the antibiotic resistance crisis. Current Opinion in Pharmacology, 2014, vol. 18, pp. 56–60. https://doi.org/10.1016/j.coph.2014.09.006
7. Michael C. A., Dominey-Howes D., Labbate M. The antimicrobial resistance crisis: causes, consequences, and management. Frontiers Public Health, 2014, vol. 2, art. 145. https://doi.org/10.3389/fpubh.2014.00145
8. Spellberg B., Srinivasan A., Chambers H. F. New societal approaches to empowering antibiotic stewardship. JAMA, 2016, vol. 315, no. 12, pp. 1229–1230. https://doi.org/10.1001/jama.2016.1346
9. Hoffman S. J., Caleo G. M., Daulaire N., Elbe S., Matsoso P., Mossialos E., Rizvi Z., Røttingen J.-A. Strategies for achieving global collective action on antimicrobial resistance. Bulletin of the World Health Organization, 2015, vol. 93, no. 12, pp. 867–876. https://doi.org/10.2471/blt.15.153171
10. Payne D. J., Miller L. F., Findlay D., Anderson J., Marks L. Time for a change: addressing R&D and commercialization challenges for antibacterials. Philosophical Transactions of the Royal Society B: Biological Sciences, 2015, vol. 370, no. 1670, pp. 20–86. https://doi.org/10.1098/rstb.2014.0086
11. Luepke K. H., Mohr J. F. The antibiotic pipeline: reviving research and development and speeding drugs to market. Expert Review of Anti-infective Therapy, 2017, vol. 15, no. 5, pp. 425–433. https://doi.org/10.1080/14787210.2017.1308251
12. Landers T., Kavanagh K. T. Is the Presidential Advisory Council on Combating Antibiotic Resistance missing opportunities. American Journal of Infection Control, 2016, vol. 44, no. 11, pp. 1356–1359. https://doi.org/10.1016/j.ajic.2016.07.008
13. Ventola C. L. The antibiotic resistance crisis: part 1: causes and threats. Pharmacy and therapeutic, 2015, vol. 40, no. 4, pp. 277–283.
14. Koszytkowska-Stawińska M., Buchowicz W. Multicomponent reactions in nucleoside chemistry. Beilstein Journal of Organic Chemistry, 2014, vol. 10, pp. 1706–1732. https://doi.org/10.3762/bjoc.10.179
15. Nizhegorodova D. B., Zafranskaya M. M., Kvasyuk E. I., Sysa A. G. Effect of emoxipine on cytotoxicity of peripheral blood mononuclears under cultivation with cytarabine and cyclocytidine. Zhurnal Belorusskogo gosudarstvennogo universiteta. Biologiya [Journal of the Belarusian State University. Biology], 2021, no. 2, pp. 3–10 (in Russian).
16. Akhrem A. A., Kalinichenko E. N., Kvasyuk E. I., Mikhailopulo I. A. Synthesis of O2, 2ʹ-cyclociditin and its 5ʹ-monophosphate. Bioorganicheskaya khimiya [Bioorganic chemistry], 1977, vol. 3, no. 6, pp. 845–847 (in Russian).
17. Travnickova E., Mikula P., Oprsal J., Bohacova M., Kubac L., Kimmer D., Soukupova J., Bittner M. Resazurin assay for assessment of antimicrobial properties of electrospun nanofiber filtration membranes. AMB Express, 2019, vol. 9, no. 1, art. 183. https://doi.org/10.1186/s13568-019-0909-z
18. Jordheim, L. P., Durantel D., Zoulim F., Dumontet Ch. Advances in the development of nucleoside and nucleotide analogues for cancer and viral diseases. Nature Reviews Drug Discovery, 2013, vol. 12, no. 6, pp. 447–464. https://doi.org/10.1038/nrd4010
19. Seley-Radtke K. L., Yates M. K. The evolution of nucleoside analogue antivirals: a review for chemists and nonchemists. Part 1: early structural modifications to the nucleoside scaffold. Antiviral Research, 2018, vol. 154, pp. 66–86. https://doi.org/10.1016/j.antiviral.2018.04.004
20. Khandazhinskaya A. L., Matyugina E., Solyev P., Wilkinson M., Buckheit K., Buckheit R. [et al]. Investigation of 5ʹ-norcarbocyclic nucleoside analogues as antiprotozoal and antibacterial agents. Molecules, 2019, vol. 24, no. 19, pp. 34–43. https://doi.org/10.3390/molecules24193433
21. Yates M. K., Seley-Radtke K. L. The evolution of antiviral nucleoside analogues: A review for chemists and nonchemists. Part II: Complex modifications to the nucleoside scaffold. Antiviral Research, 2019, vol. 162, pp. 5–21. https://doi.org/10.1016/j.antiviral.2018.11.016
22. Yang Z., Unrine J., Nonaka K., van Lanen S. G. Fe(II)-dependent, uridine-50 – monophosphate a-ketoglutarate dioxygenases in the synthesis of 50-modified nucleosides. Methods in Enzymology, 2012, vol. 516, pp. 153–168. https://doi.org/10.1016/b978-0-12-394291-3.00031-9
23. Xing L., Honda T., Fitz L., Ojima I. Fluorine in Life Sciences: Pharmaceuticals, Medicinal Diagnostics, and Agrochemicals. 4-Case studies of fluorine in drug discovery. Cambridge, 2019, pp. 181–211.
24. Sanderson K. E., MacAlister T., Costerton J. W., Cheng K.-J. Permeability of lipopolysaccharide-deficient (rough) mutants of Salmonella typhimurium to antibiotics, lysozyme, and other agents. Canadian Journal of Microbiology, 1974, vol. 20, no. 8, pp. 1135–1145.
25. Dahl T. A., Midden W. R., Hartman P. E. Pure singlet oxygen cytotoxicity for bacteria. Photochemistry and Photobiology, 1987, vol. 46, no. 3, pp. 345–352. https://doi.org/10.1111/j.1751-1097.1987.tb04779.x
26. Breijyeh Z., Jubeh B., Karaman R. Resistance of gram-negative bacteria to current antibacterial agents and approaches to resolve it. Molecules, 2020, vol. 25, no. 6, p. 1340. https://doi.org/10.3390/molecules25061340
27. Foote C. S., Denny R. W. Chemistry of singlet oxygen. VII. Quenching by P-carotene. Journal of the American Chemical Society, 1968, vol. 90, no. 22, pp. 6233–6235. https://doi.org/10.1021/ja01024a061
28. Mathews M. M., Sistrom W. R. The function of carotenoid pigments of Sarcina lutea. Archiv for Mikrobiologie, 1960, vol. 35, no. 2, pp. 139–146. https://doi.org/10.1007/bf00425002
29. Mathew-Roth M. M., Wilson T., Fujimori E., Krinsky N. I. Carotenoid chromophore length and protection against photosensitization. Photochemistry and Photobiology, 1974, vol. 19, no. 3, pp. 217–222. https://doi.org/10.1111/j.1751-1097.1974.tb06501.x
30. Krinsky N. I. Singlet excited oxygen as a mediator of the antibacterial action of leukocytes. Science, 1974, vol. 186, no. 4161, pp. 363–365. https://doi.org/10.1126/science.186.4161.363
31. Mathews-Roth M. M. Photoprotection by carotenoids. Journal of Ethnopharmacology, 1988, vol. 22, no. 3, p. 315. https://doi.org/10.1016/0378-8741(88)90245-0