Synthesis and antimicrobial activity of s-substituted derivatives of 1,2,4-triazol-3-thiol

Authors

DOI:

https://doi.org/10.15587/2519-4852.2021.235976

Keywords:

1,2,4-triazole, antibacterial activity, antifungal activity

Abstract

The aim of the work. 1,2,4-triazole derivatives possess a wide range of pharmacological activity, so they are used for the development of drugs and active pharmaceutical ingredients. Due to the reactivity of 1,2,4-triazoles there are many options for their further structural modification on different reaction centers. Therefore, the aim of the work was to obtain new S-substituted derivatives of 1,2,4-triazole-3-thiols, study physicochemical parameters of the substances synthesized, evaluate the antimicrobial activity of new S-derivatives of the 4-R1-5-((3-(pyridin-4-yl)-1H-1,2,4-triazol-5-yl)thio)methyl)-4H-1,2,4-triazole-3-thiol series, and study some regularities of the “structure – biological activity” relationship for the synthesized compounds as well.

Materials and methods. The subject of the study was new S-substituted 1,2,4-triazoles containing 2-oxopropan-1-yl and 2-aryl-2-oxoethan-1-yl substituents. The antimicrobial activity was studied by double serial dilutions on test cultures of Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), and Candida albicans (ATCC 885-653).

The results of the biological screening showed that at a concentration of 125 g/mL, all synthesized substances showed activity (MIC – in the range of 31.25 - 62.5 μg/mL, MBCK - in the range of 62.5–125 μg/mL) against strains of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans. Variation of substituents on the sulfur atom did not lead to a significant change in antimicrobial and antifungal activities among derivatives of 4-R1-5-((3-(pyridin-4-yl)-1H-1,2,4-triazole-5-yl) thio)methyl)-4H-1,2,4-triazole-3-thiols.

Conclusions. Biological screening data indicate the prospects for the search for new antimicrobial substances among the abovementioned derivatives of 1,2,4-triazoles. The most active compounds were 1-((4-ethyl-5-((3-(pyridin-4-yl)-1H-1,2,4-triazol-5-yl)thio)methyl)-4H-1,2,4-triazol-3-yl)thio)propan-2-one and 1-(4-methoxyphenyl)-2-(4-ethyl-5-(((3-(pyridin-4-yl)-1H)-1,2,4-triazol-5-yl)thio)methyl)-4H-1,2,4-triazol-3-yl)thio)ethanone, which showed the most pronounced antimicrobial activity against the Pseudomonas aeruginosa strain (MIC – 31.25 μg/mL, MBcK - 62.5 μg/mL)

Author Biographies

Yevhen Karpun, Zaporizhzhia State Medical University

Assistant

Department of Natural Sciences for Foreign Students and Toxicological Chemistry

Nataliia Polishchuk, Zaporizhzhia State Medical University

PhD, Associate Professor

Department of Microbiology, Virology and Immunology, Zaporizhzhia State Medical University

References

  1. Serwecińska, L. (2020). Antimicrobials and Antibiotic-Resistant Bacteria: A Risk to the Environment and to Public Health. Water, 12 (12), 3313. doi: http://doi.org/10.3390/w12123313
  2. Boraei, A. T. A., El Ashry, E. S. H., Duerkop, A. (2016). Regioselectivity of the alkylation of S-substituted 1,2,4-triazoles with dihaloalkanes. Chemistry Central Journal, 10 (1). doi: http://doi.org/10.1186/s13065-016-0165-0
  3. Safonov, A. A. (2018). Study acute toxicity of 4-(R-amino)-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol in vivo. Farmatsevtychnyi Zhurnal, 2, 98–101. doi: http://doi.org/10.32352/0367-3057.2.16.06
  4. Bihdan, O. A., Parchenko, V. V. (2018). Synthesis and physical-chemical properties of some 5-(3-fluorophenyl)-4-methyl-1,2,4-triazole-3-thiol derivatives. Farmatsevtychnyi Zhurnal, 2, 38–47. doi: http://doi.org/10.32352/0367-3057.2.17.05
  5. Chaudhary, P. M., Tupe, S. G., Jourwekar, S. U. et. al. (2015). Synthesis and antifungal potential of 1,2,3-triazole and 1,2,4-triazole thiol substituted strobilurin derivatives. Indian Journal of Chemistry, 54 B, 908–911.
  6. Parchenko, V. V., Parkhomenko, L. I., Izdepskyi, V. Y., Panasenko, O. I., Knysh, Ye. H. (2013). Pharmacological and biochemical characteristics of piperidine 2-(5-furan-2-yl)-4-phenyl-1,2,4-triazol-3-iltioacetate. Zaporozhye Medical Journal, 1, 39–41.
  7. Rao, D. V. N. (2015). Synthesis, Characterization and Antimicrobial Evaluation of Substituted 1,2,4-Triazole Thiones Containing Pyrazole Moiety. Journal of Clinical and Analytical Medicine, 6 (5). doi: http://doi.org/10.4328/jcam.2323
  8. Saadeh, H. A., Mosleh, I. M., Al-Bakri, A. G., Mubarak, M. S. (2010). Synthesis and antimicrobial activity of new 1,2,4-triazole-3-thiol metronidazole derivatives. Chemical Monthly, 141 (4), 471–478. doi: http://doi.org/10.1007/s00706-010-0281-9
  9. Metodychni vkazivky 9.9.5-143-2007 «Vyznachennia chutlyvosti mikroorhanizmiv do antybakterialnykh preparativ» (2007). Kyiv: MOZ Ukrainy, 63.
  10. Ding, Y., Zhang, Z., Zhang, G., Mo, S., Li, Q., Zhao, Z. (2015). Green synthesis and evaluation of the antitumor activity of a novel series of 3-[4-bi-(4-fluorophenyl)methylpiperazinyl]-4-amino-5-thione-1,2,4-triazole Schiff bases. Research on Chemical Intermediates, 42 (4), 3105–3116. doi: http://doi.org/10.1007/s11164-015-2200-5
  11. Perekhoda, L. A. (2014). Assessment of Quantitative Structure-Anticonvulsive Activity Relationships in a Series of Derivatives of 1,2,3-Triazole(1H), 1,2,4-Triazole(4H), 1,3,4-Oxadiazole(1H), and 1,3,4-Thiadiazole(1H). Pharmaceutical Chemistry Journal, 47 (11), 586–588. doi: http://doi.org/10.1007/s11094-014-1012-z
  12. Gotsulya, A. S., Mikolasyuk, O. O., Panasenko, O. I., Knysh, Ye. G. (2014). Synthesis and investigation of the physicochemical properties of 2-(5-((theophylline-7'-yl)methyl)-4-phenyl-4H-1,2,4-triazole-3-ylthio)-acetic acid salts. Zaporozhye Medical Journal, 1, 91–94. doi: http://doi.org/10.14739/2310-1210.2014.1.23820
  13. Volyanskiy, Yu. L., Gritsenko, І. S., Shirobokov, V. P. et. al. (2004). Vivchennya spetsifіchnoi aktivnostі protimіkrobnikh lіkarskikh zasobіv. Kyiv: DFTS MOZ Ukraini, 38.
  14. Hotsulia, A. S., Knysh, Y. H. (2020). Synthesis, structure and properties of 7-((4-amino-5-thio-1,2,4-triazole-3-yl)methyl)-theophylline derivatives. Current Issues in Pharmacy and Medicine: Science and Practice, 13 (2 (33)), 176–184. doi: http://doi.org/10.14739/2409-2932.2020.2.207019
  15. Bihdan, O. A., Parchenko, V. V. (2017). Physical-chemical properties of 5-(3-fluorophenyl)-4-amino-1,2,4-triazole-3-thiol s-derivatives. Current Issues in Pharmacy and Medicine: Science and Practice, 10 (2 (24)), 135–140. doi: http://doi.org/10.14739/2409-2932.2017.2.103517
  16. Zamani, K., Faghihi, K., Sangi, M. R., Zolgharnein, J. (2003). Synthesis of some new substituted 1,2,4-triazole and 1,3,4-thiadiazole and their derivatives. Turkish Journal of Chemistry, 27, 119–125.
  17. Davari, M. D., Bahrami, H., Haghighi, Z. Z., Zahedi, M. (2009). Quantum chemical investigation of intramolecular thione-thiol tautomerism of 1,2,4-triazole-3-thione and its disubstituted derivatives. Journal of Molecular Modeling, 16 (5), 841–855. doi: http://doi.org/10.1007/s00894-009-0585-z
  18. Datoussaid, Y., Othman, A., Kirsch, G. (2012). Synthesis and antibacterial activity of some 5,5’-(1,4-phenylene)-bis-1,3,4-oxadiazole and bis-1,2,4-triazole derivatives as precursors of new S-nucleosides. South African Journal of Chemistry, 65, 30–35.

Downloads

Published

2021-06-30

How to Cite

Karpun, Y., & Polishchuk, N. (2021). Synthesis and antimicrobial activity of s-substituted derivatives of 1,2,4-triazol-3-thiol. ScienceRise: Pharmaceutical Science, (3(31), 64–69. https://doi.org/10.15587/2519-4852.2021.235976

Issue

No. 3(31) (2021)

Section

Pharmaceutical Science

License

Copyright (c) 2021 Yevhen Karpun, Nataliia Polishchuk

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Our journal abides by the Creative Commons CC BY copyright rights and permissions for open access journals.