Synthesis and antimicrobial evaluation of novel 1,2,4-triazole derivatives

  • O. I. Panasenko Dnipro State Agrarian and Economic University
  • M. O. Panasenko Dnipro State Agrarian and Economic University
  • V. V. Zazharskyi Dnipro State Agrarian and Economic University
  • T. O. Samura Dnipro State Agrarian and Economic University
  • N. M. Zazharska Dnipro State Agrarian and Economic University
  • S. O. Fedotov Zaporizhzhia State Medical and Pharmaceutical University
  • A. S. Gotsulia Zaporizhzhia State Medical and Pharmaceutical University
  • O. O. Maliugina Zaporizhzhia State Medical and Pharmaceutical University
  • T. S. Brytanova Zaporizhzhia State Medical and Pharmaceutical University
  • B. V. Gutyj Stepan Gzhytskyi National University of Veterinary Medicine and Biotechnologies
  • V. P. Martynyshyn Stepan Gzhytskyi National University of Veterinary Medicine and Biotechnologies
DOI: https://doi.org/10.15421/0225132
Keywords: properties, growth inhibition zone, bacterial colonies, multidrug-resistant strain.

Abstract

Derivatives of 1,2,4-triazole are widely recognized as promising scaffolds for the development of biologically a c tive compounds, particularly those exhibiting antimicrobial properties. In the present study, the antimicrobial potential of a series of newly synthesized 1,2,4-triazole-based heterocyclic compounds was investigated using the in vitro disk diffusion method against 15 clinically significant bacterial strains, including both Gram-positive and Gram-negative species. The compounds were dissolved in 70% ethanol and tested at different concentrations to assess their spectrum and degree of antibacterial activity. One compound, ethyl 2-((3-mercapto-9-methylpyrazolo[1,5-d][1,2,4]triazolo[3,4-f][1,2,4]triazin-6-yl)thio)acetate, exhibited the most pronounced inhibitory effect, producing zones of bacterial growth inhibition exceeding 8 mm in diameter in 14 out of the 15 tested bacterial strains. Several other derivatives, particula r ly those bearing N-ethyl or N-phenyl substitutions within triazolothiadiazole frameworks, as well as dichlorophenyl-substituted triazolothiadiazines, exhibited moderate antibacterial activity, inhibiting the growth of five to seven ba c terial strains depending on their structural features. The structure – activity relationship analysis suggests that the pre s ence of electron-withdrawing groups, fused heterocyclic systems and s ulfur-containing linkages may contribute to enhanced biological activity. Overall, the results underscore the importance of the 1,2,4-triazole core in the design of novel antimicrobial agents and provide a solid foundation for further structural optimization and pharmaceutical d e velopment of these compounds.

References

Berida, T., McKee, S. R., Chatterjee, S., Manning, D. L., Li, W., Pandey, P., Tripathi, S. K., Mreyoud, Y., Smirnov, A., Doerksen, R. J., Jackson, M., Ducho, C., Stallings, C. L., & Roy, S. (2023). Discovery, synthesis, and optimization of 1,2,4-triazolyl pyridines targeting Mycobacterium tuberculosis. ACS Infectious Diseases, 9(11), 2282–2298.

Bihdan, O. A. (2021). Protymikrobna ta protyhrybkova aktyvnist’ novykh ftorfenilvmisnykh 1,2,4-tryazoliv [Antimicrobial and antifungal activity of new fluorophenyl-containing 1,2,4-triazoles]. Farmatsevtychnyi Zhurnal, 76(2), 87–93 (in Ukrainian).

Fedotov, S. O., & Hotsulia, A. S. (2021). Synthesis and properties of S-derivatives of 4-amino-5-(5-methylpyrazol-3-yl)-1,2,4-triazole-3-thiol. Current Issues in Pharmacy and Medicine: Science and Practice, 14(3), 268–274.

Fedotov, S. O., & Hotsulia, A. S. (2023). Synthesis and properties of S-alkyl 4-amino-5-(5-(3-fluorophenyl)-pyrazol-3-yl)-1,2,4-triazole-3-thiol derivatives. Current Issues in Pharmacy and Medicine: Science and Practice, 16(1), 5–11.

Gao, F., Wang, T., Xiao, J., & Huang, G. (2019). Antibacterial activity study of 1,2,4-triazole derivatives. European Journal of Medicinal Chemistry, 173, 274–281.

Gotsulya, A., Zazharskyi, V., Davydenko, P., Kulishenko, O., Parchenko, V., & Brytanova, T. (2022). N’-(2-(5-((Theophylline-7-yl)methyl)-4-ethyl-1,2,4-triazole-3-ylthio)acetyl) isonicotinohydrazide as antitubercular agents. Hacettepe University Journal of the Faculty of Pharmacy, 42(3), 149–155.

Guan, Q., Xing, S., Wang, L., Zhu, J., Guo, C., Xu, C., Zhao, Q., Wu, Y., Chen, Y., & Sun, H. (2024). Triazoles in medicinal chemistry: Physicochemical properties, bioisosterism, and application. Journal of Medicinal Chemistry, 67(10), 7788–7824.

Joshi, R., Pandey, N., Yadav, S. K., Tilak, R., Mishra, H., & Pokharia, S. (2018). Synthesis, spectroscopic characterization, DFT studies and antifungal activity of (E)-4-amino-5-[N'-(2-nitro-benzylidene)-hydrazino]-2,4-dihydro-[1,2,4]triazole-3-thione. Journal of Molecular Structure, 1164, 386–403.

Kaproń, B., Łuszczki, J. J., Płazińska, A., Siwek, A., Karcz, T., Gryboś, A., Nowak, G., Makuch-Kocka, A., Walczak, K., Langner, E., Szalast, K., Marciniak, S., Paczkowska, M., Cielecka-Piontek, J., Ciesla, L. M., & Plech, T. (2019). Development of the 1,2,4-triazole-based anticonvulsant drug candidates acting on the voltage-gated sodium channels. Insights from in-vivo, in-vitro, and in-silico studies. European Journal of Pharmaceutical Sciences, 129, 42–57.

Khomenko, K. V. (2024). Some issues of antimicrobial and antifungal activity of 1,2,4-triazole derivatives (literature review). Ukrainian Journal of Military Medicine, 5(1), 124–131.

Pachuta-Stec, A. (2022). Antioxidant activity of 1,2,4-triazole and its derivatives: A mini-review. Mini-Reviews in Medicinal Chemistry, 22(7), 1081–1094.

Qi, L., Li, M. C., Bai, J. C., Ren, Y. H., & Ma, H. X. (2021). In vitro antifungal activities, molecular docking, and DFT studies of 4-amine-3-hydrazino-5-mercapto-1,2,4-triazole derivatives. Bioorganic and Medicinal Chemistry Letters, 40, 127902.

Shaykoon, M. S., Marzouk, A. A., Soltan, O. M., Wanas, A. S., Radwan, M. M., Gouda, A. M., Youssif, B. G. M., & Abdel-Aziz, M. (2020). Design, synthesis and antitrypanosomal activity of heteroaryl-based 1,2,4-triazole and 1,3,4-oxadiazole derivatives. Bioorganic Chemistry, 100, 103933.

Strzelecka, M., & Świątek, P. (2021). 1,2,4-Triazoles as important antibacterial agents. Pharmaceuticals, 14(3), 224.

Wen, X., Zhou, Y., Zeng, J., & Liu, X. (2020). Recent development of 1,2,4-triazole-containing compounds as anticancer agents. Current Topics in Medicinal Chemistry, 20(16), 1441–1460.

Youssef, M. F., Nafie, M. S., Salama, E. E., Boraei, A. T. A., & Gad, E. M. (2022). Synthesis of new bioactive indolyl-1,2,4-triazole hybrids as dual inhibitors for EGFR/PARP-1 targeting breast and liver cancer cells. ACS Omega, 7(49), 45665–45677.

Zazharskyi, V. V., Bigdan, O. A., Parchenko, V. V., Karpenko, Y. V., Zazharska, N. M., Mykhailiuk, Y. O., Kulishenko, O. M., Davydenko, P. O., Kulish, S. M., & Gutyj, B. V. (2024). Toxicity parameters of a new 1,2,4-triazole derivative when subcutaneously injected to guinea pigs. Regulatory Mechanisms in Biosystems, 15(1), 166–170.

Zazharskyi, V., Bigdan, O., Parchenko, V., Parchenko, M., Fotina, T., Davydenko, P., Kulishenko, O., Zazharskaya, N., & Borovik, I. (2021). Antimicrobial activity of some furans containing 1,2,4-triazoles. Archives of Pharmacy Practice, 12(2), 60–65.

Published
2025-07-24
How to Cite
Panasenko, O. I., Panasenko, M. O., Zazharskyi, V. V., Samura, T. O., Zazharska, N. M., Fedotov, S. O., Gotsulia, A. S., Maliugina, O. O., Brytanova, T. S., Gutyj, B. V., & Martynyshyn, V. P. (2025). Synthesis and antimicrobial evaluation of novel 1,2,4-triazole derivatives. Regulatory Mechanisms in Biosystems, 16(3), e25132. https://doi.org/10.15421/0225132
Issue
Vol 16 No 3 (2025): Regulatory Mechanisms in Biosystems
Section
Статті

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