Current research trends of 1,2,4-triazole derivatives biological activity (literature review)

Authors

DOI:

https://doi.org/10.14739/2409-2932.2025.2.322344

Keywords:

derivatives 1,2,4-triazole, biological activity

Abstract

The relevance of searching for new active compounds among 1,2,4-triazole derivatives is determined by their potential effectiveness in treating various diseases such as cancer, inflammation, microbial infections, and antioxidant disorders. Studies show that these compounds can inhibit the proliferation of cancer cells, exhibit anti-inflammatory properties, demonstrate activity against pathogenic microorganisms, and neutralize free radicals, which is important for preventing oxidative stress. Therefore, the study of 1,2,4-triazole derivatives may lead to the development of new effective drugs, which is extremely relevant in modern medicine.

The aim of the work is to summarize recent scientific advances in the study of 1,2,4-triazole derivatives, particularly their antitumor, antimicrobial, anti-inflammatory, anticonvulsant, and antioxidant activity, to substantiate their potential as multifunctional therapeutic agents in modern medicine.

Results. The literature review confirmed that 1,2,4-triazole derivatives exhibit significant biological activity across various therapeutic areas. Studies revealed high antitumor efficacy of hybrid compounds, particularly the derivative 5-((4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)methyl)-4-(4-nitrophenyl)-4H-1,2,4-triazole-3-thiol, which demonstrated notable activity against breast cancer cells (MCF-7), as confirmed by DFT and molecular docking methods. In antimicrobial therapy, derivatives combined with norfloxacin showed higher efficacy compared to standard antibiotics against both Gram-positive and Gram-negative bacteria while maintaining good biocompatibility. Research on anticonvulsant properties found that 4-amino-4H-1,2,4-triazole derivatives effectively interact with the GABA-A receptor, outperforming the standard drug phenytoin in in vivo models. In anti-inflammatory studies, compounds containing a 1,3,4-thiadiazine fragment achieved 91 % inhibition of edema, surpassing ibuprofen (82 %), and reduced key inflammatory biomarkers. The antioxidant properties of brominated [1,2,4]triazolo[1,5-a]pyridine derivatives were particularly pronounced, with maximum activity observed at a concentration of 150 μg/mL. These results highlight the broad therapeutic potential of 1,2,4-triazole derivatives, making them promising candidates for the development of novel drugs to combat oncological, infectious, inflammatory, and neurodegenerative diseases, as well as for oxidative stress prevention.

Conclusions. 1,2,4-Triazole derivatives exhibit a wide range of biological activity, including antifungal, antimicrobial, anticancer, antibacterial, anticonvulsant, anti-inflammatory, and antioxidant properties. This indicates their potential as versatile agents for the treatment of various diseases.

Author Biographies

I. M. Bilai, Zaporizhzhia State Medical and Pharmaceutical University

MD, PhD, DSc, Professor, Head of the Department of Clinical Pharmacy, Pharmacotherapy, Pharmacognosy and Pharmaceutical Chemistry

V. I. Dariy, Zaporizhzhia State Medical and Pharmaceutical University

MD, PhD, DSc, Professor of the Department of Neurology

A. V. Khilkovets, Zaporizhzhia State Medical and Pharmaceutical University

PhD, Assistant of the Department of Clinical Pharmacy, Pharmacotherapy, Pharmacognosy and Pharmaceutical Chemistry

A. I. Bilai, Zaporizhzhia State Medical and Pharmaceutical University

MD, PhD, Associate Professor of the Department of Faculty Surgery

References

  1. Karpun Y, Parchenko V, Fotina T, Demianenko D, Fotin A, Nahornyi V, et al. The investigation of antimicrobial activity of some s-substituted bis-1,2,4-triazole-3-thiones. Pharmacia. 2021;68(4):797-804. doi: https://doi.org/10.3897/pharmacia.68.e65761
  2. Karpun EO, Parchenko VV. [Synthesis, physicochemical properties and antigypoxic activity of some S-derivatives of 4-alkyl-5-(((3-(pyridin-4-yl)-1H-1,2,4-triazol-5-yl)thio)methyl)-4H-1,2,4-triazole-3-thiol]. Farmatsevtychnyi zhurnal. 2020;75(6):56-64. Ukrainian. doi: https://doi.org/10.32352/0367-3057.6.20.06
  3. Pagniez F, Lebouvier N, Na YM, Ourliac-Garnier I, Picot C, Le Borgne M, et al. Biological exploration of a novel 1,2,4-triazole-indole hybrid molecule as antifungal agent. J Enzyme Inhib Med Chem. 2020;35(1):398-403. doi: https://doi.org/10.1080/14756366.2019.1705292
  4. Kryvenko BI, Kolesnyk MY, Belenichev IF, Kucherenko LI, Mazur IA, Yadlovskyi OE, et al. [Thiotriazolin in improving the effectiveness and safety of complex treatment of Covid-19]. Novyny medytsyny ta farmatsiyi v Ukraini. 2022;(2):6-10. Ukrainian. Available from: http://dspace.zsmu.edu.ua/handle/123456789/16926
  5. Khilkovets AV, Bilai IM. Study of acute toxicity of new thiophene-containing derivatives of 1,2,4-triazole. Zaporozhye medical journal. 2023;25(1):46-9. doi: https://doi.org/10.14739/2310-1210.2023.1.266318
  6. Kalchenko VV, Shcherbyna RO. [Computer prediction of toxicity of new S-alkyl derivatives of 1,2,4-triazole]. Current issues in pharmacy and medicine: science and practice. 2024;17(3):253-6. doi: https://doi.org/10.14739/2409-2932.2024.3.312927
  7. Samvelyan MA, Ghochikyan TV, Yeganyan TH, Sarfraz M, Jakob C. Synthesis and study of the nematocidal activity of 1,2,4-triazolo-1,2,4-triazoles. Proceedings of the YSU B: Chemical and Biological Sciences. 2020;54(1):3-11. doi: https://doi.org/10.46991/PYSU:B/2020.54.1.003
  8. Shoman M, Soltan O, Nagaoka K, Abdel-aziz S, Narumi A, Konno H, et al. Design, synthesis, molecular modeling and biological evaluation of novel 1,5-diarylpyrazole carboxamide derivatives as antiproliferative agents. J Adv Biomed Pharm Sci. 2021;4(3):152-9.
  9. Gupta O, Pradhan T, Chawla G. An updated review on diverse range of biological activities of 1,2,4-triazole derivatives: Insight into structure activity relationship. J Mol Struct. 2023;1274(Part 2):134487. doi: https://doi.org/10.1016/j.molstruc.2022.134487
  10. Liao L, Jiang C, Chen J, Shi J, Li X, Wang Y, et al. Synthesis and biological evaluation of 1,2,4-triazole derivatives as potential neuroprotectant against ischemic brain injury. Eur J Med Chem. 2020;190:112114. doi: https://doi.org/10.1016/j.ejmech.2020.112114
  11. Slaihim MM, Al-Suede FS, Khairuddean M, Sultan SB, Nazari M, Ahamed MB, et al. Antitumor activity and synthesis of new derivatives with fused ring system of 1,2,4-triazole scaffold and their characterization. J Mol Struct. 2023;1289:135834. doi: https://doi.org/10.1016/j.molstruc.2023.135834
  12. Alam MM. 1,2,3-Triazole hybrids as anticancer agents: A review. Arch Pharm (Weinheim). 2022 Jan;355(1):e2100158. doi: https://doi.org/10.1002/ardp.202100158
  13. Dwarakanath D, Kulal A, Basappa B, Xi Z, Pandey V, Bharath Br, et al. Synthesis, computational studies and evaluation of benzisoxazole tethered 1,2,4-triazoles as anticancer and antimicrobial agents. J Mol Struct. 2024;1308:138070. doi: https://doi.org/10.1016/j.molstruc.2024.138070
  14. Aouad MR, Al-Mohammadi HM, Al-Blewi FF, Ihmaid S, Elbadawy HM, Althagfan SS, et al. Introducing of acyclonucleoside analogues tethered 1,2,4-triazole as anticancer agents with dual epidermal growth factor receptor kinase and microtubule inhibitors. Bioorg Chem. 2020;94:103446. doi: https://doi.org/10.1016/j.bioorg.2019.103446
  15. Wang C, Li Y, Liu T, Wang Z, Zhang Y, Bao K, et al. Design, synthesis and evaluation of antiproliferative and antitubulin activities of 5-methyl-4-aryl-3-(4-arylpiperazine-1-carbonyl)-4H-1,2,4-triazoles. Bioorg Chem. 2020;104:103909. doi: https://doi.org/10.1016/j.bioorg.2020.103909
  16. Strzelecka M, Świątek P. 1,2,4-Triazoles as Important Antibacterial Agents. Pharmaceuticals (Basel). 2021;14(3):224. doi: https://doi.org/10.3390/ph14030224
  17. Al-Sa’doni HH, Delmani F-A, Al Balushi AM, Al-Ahmad AH, Alsawakhneh SO, Al-Soud YA. Synthesis and antibacterial activity of some new 1,2,4-triazole derivatives bearing carbohydrazide moiety. Eur J Chem. 2020;11(2):113-9. doi: https://doi.org/10.5155/eurjchem.11.2.113-119.1968
  18. Yang P, Luo JB, Wang ZZ, Zhang LL, Feng J, Xie XB, et al. Synthesis, molecular docking, and evaluation of antibacterial activity of 1,2,4-triazole-norfloxacin hybrids. Bioorg Chem. 2021;115:105270. doi: https://doi.org/10.1016/j.bioorg.2021.105270
  19. Karpun Y, Polishchuk N. Synthesis and antimicrobial activity of s-substituted derivatives of 1,2,4-triazol-3-thiol. ScienceRise: Pharmaceutical Science. 2021;(3):64-9. doi: https://doi.org/10.15587/2519-4852.2021.235976
  20. Ghosh S, Sinha JK, Ghosh S, Sharma H, Bhaskar R, Narayanan KB. A Comprehensive Review of Emerging Trends and Innovative Therapies in Epilepsy Management. Brain Sci. 2023;13(9):1305. doi: https://doi.org/10.3390/brainsci13091305
  21. Spanoghe J, Larsen LE, Craey E, Manzella S, Van Dycke A, Boon P, et al. The Signaling Pathways Involved in the Anticonvulsive Effects of the Adenosine A1 Receptor. Int J Mol Sci. 2020;22(1):320. doi: https://doi.org/10.3390/ijms22010320
  22. Jain R, Prabitha P, Kashaw SK, Jain V, Kohli DV. Design, synthesis, in silico studies, and pharmacological evaluation of 5-aryl-4-(chloroacetylamino)-3-mercapto-1,2,4-triazole derivatives as anticonvulsant agents. Int J Appl Pharm. 2024;16(6):190-200. doi: https://doi.org/10.22159/ijap.2024v16i6.52379
  23. Lingappa M, Guruswamy V, Bantal V. Synthesis and characterization of 4-amino-4H-1,2,4-triazole derivatives: Anticonvulsant activity. Curr Chem Lett. 2021;9:33-42. doi: https://doi.org/10.5267/j.ccl.2020.7.002
  24. Krasovska NI, Kopteva SD, Posudiievska OR, Kyrylakha SV, Okovytyy SI, et al. Methods of synthesis of quinazolines and their condensed analogues – potential anti-inflammatory agents (review). Journal of Chemistry and Technologies. 2023;31(2):385-410. doi: https://doi.org/10.15421/jchemtech.v31i2.280199
  25. Sharma S, Kumar D, Singh G, Monga V, Kumar B. Recent advancements in the development of heterocyclic anti-inflammatory agents. Eur J Med Chem. 2020 Aug 15;200:112438. doi: https://doi.org/10.1016/j.ejmech.2020.112438
  26. Shahid W, Ashraf M, Saleem M, Bashir B, Muzaffar S, Ali M, et al. Exploring phenylcarbamoylazinane-1,2,4-triazole thioethers as lipoxygenase inhibitors supported with in vitro, in silico and cytotoxic studies. Bioorg Chem. 2021;115:105261. doi: https://doi.org/10.1016/j.bioorg.2021.105261
  27. Jeedi NM, Bajji S, Ronad PM, Nimbal SK, Patil SB. Analgesic and anti-inflammatory investigation of 1,2,4- triazole derivatives in rats. J Med Pharm Allied Sci. 2023;12(3):5850-8. doi: https://doi.org/10.55522/jmpas.V12I3.4666
  28. Pachuta-Stec A. Antioxidant Activity of 1,2,4-Triazole and its Derivatives: A Mini-Review. Mini Rev Med Chem. 2022;22(7):1081-94. doi: https://doi.org/10.2174/1389557521666210401091802
  29. Fouad M. Design, synthesis, and antioxidant activity screening of some new thiazole and pyrazolo[5,1-c][1,2,4]triazole derivatives. ChemRxiv. 2023. doi: https://doi.org/10.26434/chemrxiv-2023-557bw
  30. Smolsky O, Makei O, Yanchenko V, Poletai V. Synthesis and preclinical study of antioxidant activity of [1,2,4]triazolo[1,5-a]pyridine derivatives. BHT: Biota, Human, Technology. 2022;2:129-41. Available from: http://erpub.chnpu.edu.ua:8080/jspui/handle/123456789/9456
  31. AL-Tamimi MB, Al-Majidi SM. Synthesis, identification of some new 1,2,4-triazole derivatives from 6-amino-1,3-dimethyluracil and evaluation of their molecular docking, Anti-oxidant and experimental. Int J Health Sci. 2020;6(6):7185-203. doi: https://doi.org/10.53730/ijhs.v6nS6.12019

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2025-07-04

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1.
Bilai IM, Dariy VI, Khilkovets AV, Bilai AI. Current research trends of 1,2,4-triazole derivatives biological activity (literature review). Current issues in pharmacy and medicine: science and practice [Internet]. 2025Jul.4 [cited 2026Jun.29];18(2):197-205. Available from: https://pharmed.zsmu.edu.ua/article/view/322344

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Vol. 18 No. 2 (2025)

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Review

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Copyright (c) 2025 I. M. Bilai, V. I. Dariy, A. V. Khilkovets, A. I. Bilai

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