Study of acute toxicity of new thiophene-containing derivatives of 1,2,4-triazole

Authors

DOI:

https://doi.org/10.14739/2310-1210.2023.1.266318

Keywords:

acute toxicity, rats, 1,2,4-triazole derivatives

Abstract

Acute toxicity studies are an integral part of preclinical studies of any new biologically active compound. It should be noted that it is this stage of research that is crucial regarding the possibility of further use of a pharmacologically active substance as a drug. This indicator also helps to determine the initial dose for clinical trials and establish a range of potentially safe doses. The data obtained will help determine the direction of new chemical syntheses, replenish the relevant libraries in silico, as well as reveal many other fundamentally important parameters that characterize the interaction in the compound – living organism system.

The aim of this research is to study the acute toxicity of 2-((4-phenyl-5-(thiophene-3-ylmethyl)-1,2,4-triazole-3-yl)thio)sodium acetate.

Materials and methods. Previously, a prediction was made using the GUSAR computer program, which helped determine the dose intervals. Acute toxicity was determined by the experimental method of Kerber in vivo using white nonlinear Wistar rats. The rats were weighed, labeled, and divided into five groups of six individuals of each.

Results. After the introduction of compound moving activity decreased, drowsiness, pupil miosis, and thirst were observed. In the fifth group, with the maximum dilution, all rats died within two hours after administration of the test compound. During the death, convulsions were observed. In the fourth group five animals died, and in the third – two rats died. In the first two groups, all the rats survived. During follow-up, the animals behaved normally. Based on the results of the research, calculations were made and the LD50 indicator was determined.

Conclusions. According to the results, the studied compound belonged to the V class of toxicity (almost non-toxic), and the resulting LD50 value was 1125 mg/kg. This indicator confirmed the prospects for further study of this compound.

Author Biographies

A. V. Khilkovets, Zaporizhzhia State Medical University, Ukraine

PhD-student of the Department of Natural Sciences for Foreign Students and Toxicological Chemistry, Assistant of the Department of Clinical Pharmacy, Pharmacotherapy, Pharmacognosy and Pharmaceutical Chemistry

I. M. Bilai, Zaporizhzhia State Medical University, Ukraine

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

References

Liu, Z., Dang, K., Gao, J., Fan, P., Li, C., Wang, H., Li, H., Deng, X., Gao, Y., & Qian, A. (2022). Toxicity prediction of 1,2,4-triazoles compounds by QSTR and interspecies QSTTR models. Ecotoxicology and environmental safety, 242, 113839. https://doi.org/10.1016/j.ecoenv.2022.113839

Opsomer, T., & Dehaen, W. (2022). 1,2,4-Triazoles. In Comprehensive Heterocyclic Chemistry IV (pp. 78-121). Elsevier. https://doi.org/10.1016/b978-0-12-409547-2.14854-1

Shcherbyna, R. O., Danilchenko, D. M., Parchenko, V. V., Panasenko, O. I., Knysh, E. H., Hromyh, N. A., & Lyholat, Y. V. (2017). Studying Of 2-((5-R-4-R-1-4H-1,2,4-Triazole-3-Yl)Thio)Acetic Acid Salts Influence On Growth And Progress Of Blackberries (KIOWA Variety) Propagules. Research Journal of Pharmaceutical Biological and Chemical Sciences, 8(3), 975-979.

Kaplaushenko, A. H., Parchenko, V. V., Panasenko, O. I., Knysh, Ye. H., & Darii, K. V. (2008). Syntez i hostra toksychnist solei 2-[(5-R-4-R1-1,2,4-triazol-3-iltio)-2-(karboksymetyltio)karbonotioil] hidrazynoatsetatnykh kyslot [Synthesis and acute toxicity of salts of 2-[(5-R-4-R1-1,2,4-triazole-3-ylthio)-2-(carboxymethylthio)-carbonothioyl]hydrazinoacetate acids]. Current issues of pharmaceutical and medical science and practice, 21, (Vol. 2, pp. 87-92). [in Ukrainian].

Bigdan, O. (2021). Toxicity of Substance BKP-115 on Rats and Mice of Both Sexes at Long Term Intragastric Introduction. Archives of Pharmacy Practice, 12(2), 6-11. https://doi.org/10.51847/v8mvj5iqgt

Bielenichev, I. F., Vizir, V. A., Mamchur, V. Yo., & Kuriata, O. V. (2019). Mesto tiotriazolina v galeree sovremennykh metabolitotropnykh lekarstvennykh sredstv [Place of tiotriazoline in the gallery of modern metabolitotropic medicines]. Zaporozhye medical journal, 21(1), 119-128. [in Russian]. https://doi.org/10.14739/2310-1210.2019.1.155856

Belenichev, I., Kucherenko, L., Pavlov, S., Bukhtiyarova, N., Popazova, O., Derevianko, N., & Nimenko, G. (2022). Therapy of post-COVID-19 syndrome: improving the efficiency and safety of basic metabolic drug treatment with tiazotic acid (thiotriazoline). Pharmacia, 69(2), 509-516. https://doi.org/10.3897/pharmacia.69.e82596

Belenichev, I., Kucherenko, L., Nagornaya, E., Mazur, I., Bidnenko, A., Bukhtiyarova, N., & Avramenko, N. (2015). Functional nitric oxide conjugate systems state/restored heart thiols of rats in modeling isadrine-pituitrin’s myocardial infarction using metabolite-tropic cardioprotector “Angiolin”. International Journal of Basic & Clinical Pharmacology, 4(1), 15-21. https://doi.org/10.5455/2319-2003.ijbcp20150238

Belenichev, I. F., Aliyeva, E. G., Kamyshny, O. M., Bukhtiyarova, N. V., Ryzhenko, V. P., & Gorchakova, N. O. (2022). Pharmacological Modulation of Endogenous Neuroprotection after Experimental Prenatal Hypoxia. Neurochemical Journal, 16(1), 68-75. https://doi.org/10.1134/s1819712422010044

(1999). Direktiva Soveta ES o sblizhenii zakonov, postanovlenii i administrirovanie polozhenii gosudarstv ES po voprosam zashchity zhivotnykh, ispol'zuemykh dlya eksperimental'nykh i drugikh nauchnykh tselei (86/609/EES) [Directive of the Council of the EU on the convergence of laws, decrees and administrations of the EU states on the protection of animals used for experimental and other scientific purposes (86/609/EEC)]. In N. A. Lyapunov, V. A. Zagorii, V. P. Georgievskii, & E. P. Bezuglaya (Eds.), Nadlezhashchaya proizvodstvennaya praktika lekarstvennykh sredstv [Appropriate production practice of medicinal products] (pp. 508-545). Morion. [in Russian].

Stefanov, O. V. (Ed.). (2001). Doklinichni doslidzhennia likarskykh zasobiv [Preclinical studies of medicinal products: methodical recommendations]. Kyiv: Avicena. [in Ukrainian].

Bak, P. G., Belenichev, I. F., Kucherenko, L. I., Abramov, A. V., & Khromylova, O. V. (2021). Morpho-functional indicators changes of rats’ myocardium in experimental doxorubicin-induced chronic heart failure and its pharmacological modulation with new 4-amino-1,2,4-triazole derivative. Pharmacia, 68(4), 919-925. https://doi.org/10.3897/pharmacia.68.e75298

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Published

2023-03-06

How to Cite

1.
Khilkovets AV, Bilai IM. Study of acute toxicity of new thiophene-containing derivatives of 1,2,4-triazole. Zaporozhye Medical Journal [Internet]. 2023Mar.6 [cited 2024Nov.22];25(1):46-9. Available from: http://zmj.zsmu.edu.ua/article/view/266318