Study of The Stress-Protective Effect of Sodium 2-((4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazol-3-yl)thio)acetate

Andrii Safonov; Denys Demianenko; Yevgenia Vashchyk; Dmytro Lytkin; Olha Polonets; Albina Kosareva; Lyubov Morozova

doi:10.52794/hujpharm.1374871

Research Article

Study of The Stress-Protective Effect of Sodium 2-((4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazol-3-yl)thio)acetate

Year 2024, Volume: 44 Issue: 2, 143 - 152, 01.06.2024

Andrii Safonov , Denys Demianenko , Yevgenia Vashchyk , Dmytro Lytkin , Olha Polonets , Albina Kosareva , Lyubov Morozova

https://doi.org/10.52794/hujpharm.1374871

Abstract

The aim was to study the stress-protective effect of sodium 2-((4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazol-3-yl)thio)acetate. The analysis of the effect of the sample on the behavior and psycho-emotional state of animals, physiological parameters, antioxidant-prooxidant system was studied. Studies of stress-protective properties were performed on white outbred rats. As a comparison drug was used a Mebicar (Adaptol®) (reference sample).
One hour after the simulation of immobilization 6-hour stress, the animals were subjected to a series of tests: "Open Field", "Light and Dark Chamber", "Morris Water Labyrinth". Behavioral tests were performed according to generally accepted methods in simplified modifications. Serum and liver homogenate were used to determine the content of markers of the antioxidant-prooxidant system: quantitative content of diene conjugates (DC), thiobarbituric acid reactants (TBA reactants), as well as catalase and superoxide dismutase (SOD) activity.
Based on complex behavioral tests data, Catalase, TBA reactants, DC, SOD data in the serum and in the liver homogenate it can be concluded the presence of stress-protective properties of sodium 2-((4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazol-3-yl)thio)acetate in the model of acute immobilization stress.

Keywords

1.2.4-triazole, acute immobilization stress, heterocyclic compounds

Ethical Statement

Hereby, I Andrii Safonov consciously assure that for the manuscript “Study Of The Stress-Protective Effect Of Sodium 2-((4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazol-3-yl)thio)acetate” the following is fulfilled: 1) This material is the authors' own original work, which has not been previously published elsewhere. 2) The paper is not currently being considered for publication elsewhere. 3) The paper reflects the authors' own research and analysis in a truthful and complete manner. 4) The paper properly credits the meaningful contributions of co-authors and co-researchers. 5) The results are appropriately placed in the context of prior and existing research. 6) All sources used are properly disclosed (correct citation). Literally copying of text must be indicated as such by using quotation marks and giving proper reference. 7) All authors have been personally and actively involved in substantial work leading to the paper, and will take public responsibility for its content.

Thanks

The authors are highly thankful to the The Ministry of Education and Science of Ukraine for financial support which was given according to scientific topic № 0120U101649 "Synthesis, modification and study of the properties of 1,2,4-triazole derivatives for the purpose of antimicrobial drug production".

References

1. Calcia MA, Bonsall DR, Bloomfield PS, Selvaraj S, Barichel- lo T, Howes OD. Stress and neuroinflammation: A systematic review of the effects of stress on microglia and the implications for mental illness. Psychopharmacology. 2016;233:163750. https://doi.org/10.1007/s00213-016-4218-9
2. Liu YZ, Wang YX, Jiang CL. Inflammation: The common pathway of stress-related diseases. Front Hum Neurosci. 2017;11:316. https://doi.org/10.3389/fnhum.2017.00316
3. Liberman AC, Trias E, da Silva Chagas L, Trindade P, dos Santos Pereira M, Refojo D, et al. Neuroimmune and inflammatory signals in complex disorders of the central nervous system. Neuroimmunomodulation. 2018;25:246-70. https://doi.org/10.1159/000494761
4. Kim IB, Lee JH, Park SC. The relationship between stress, inflammation, and depression. Biomedicines. 2022;10(8):1929. https://doi.org/10.3390/biomedicines10081929
5. Kovalenko VM . Compendium 2019 - medicinal products. Kyiv: MORION; 2019. 2480. Available from: https://compen- dium.com.ua
6. Sameliuk Y, Kaplaushenko T, Al Zedan F. 1,2,4-triazole de- rivatives in medicine and pharmacy and application pros- pects. Ankara Ecz Fak Derg. 2021;45(3):598-614. https://doi.org/10.33483/jfpau.885888
7. Shcherbyna R. Microwave-assisted synthesis of some new derivatives of 4-substituted-3-(morpholinomethyl)-4h-1,2,4-triazole-5-thioles. Ankara Ecz Fak Derg. 2019;43(3):220-9. https://doi.org/10.33483/jfpau.533166
8. Safonov A. Microwave synthesis of new N-R-3-(alkylthio)-5-(thiophen-2-ylmethyl)-1,2,4-triazol-4-amines. Ankara Ecz Fak Derg. 2020;44(1):89-98. https://doi.org/10.33483/jfpau.620599
9. Shcherbyna R, Panasenko A, Knysh E, Varinsky B. Synthesis and physicochemical properties of 2-((4-R-3-(morpholinomethylene)-4H-1,2,4-triazol-5-yl)thio)acetic acids. Aktualʹnì Pitannâ Farmacevtičnoï ì Medičnoï Nauki ta Praktiki. 2014;3(16):18-21. https://doi.org/10.14739/24092932.2014.3.30016
10. Ihnatova T, Kaplaushenko A, Frolova Yu, Pryhlo E. Synthesis and antioxidant properties of some new 5-phenethyl-3-thio-1,2,4-triazoles. Pharmacia. 2021;68(1):129-33. https://doi.org/10.3897/pharmacia.68.e53320
11. Shcherbyna R, Parchenko V, Varynskyi B, Kaplaushenko A. The development of HPLC-DAD method for determination of active pharmaceutical ingredient in the potassium 2-((4-amino-5-(morpholinomethyl)-4H-1,2,4-triazol-3-yl) thio)acetate substance. Current Issues in Pharmacy and Medical Sciences. 2019;32(1):5-9. https://doi.org/10.2478/cipms-2019-0001
12. Frolova Y, Kaplaushenko A, Nagornaya N. Design, synthesis, antimicrobial and antifungal activities of new 1,2,4-tri- azole derivatives containing 1H-tetrazole moiety. Ankara Ecz Fak Derg. 2020;44(1):70-88. https://doi.org/10.33483/jfpau.574001
13. Shcherbyna R. An investigation of the pharmacokinetics and potential metabolites of potassium 2-((4-amino-5- (morfolinometyl)-4H-1,2,4-triazol-3-yl) thio) acetate on rats. Ankara Ecz Fak Derg. 2020;44(2):233-41. https://doi.org/10.33483/jfpau.681611
14. Shcherbyna R, Vashchyk Y. The research of 1,2,4-triazole derivatives hepatoprotective activity under tetracycline and infectious hepatitis. Ankara Ecz Fak Derg. 2019;43(2):135-46. https://doi.org/10.33483/jfpau.487173
15. Gotsulya A. Synthesis and antiradical activity of alkyl derivatives of 5-(5-methyl-1H-pyrazol-3-yl)-4-phenyl-4H-1,2,4-triazole-3-thiol. Ankara Ecz Fak Derg. 2020;44 (2):211-9 https://doi.org/10.33483/jfpau.616116
16. Gotsulya A, Zaika Y, Brytanova T. Synthesis, properties and biological potential some condensed derivatives 1,2,4-triazole. Ankara Ecz Fak Derg. 2022;46(2):308-21. https://doi.org/10.33483/jfpau.971602
17. Samelyuk Y, Kaplaushenko A. Synthesis of 3-alkylthio (sulfo)-1,2,4-triazoles, Containing methoxyphenyl substituents at C5 atoms, their antipyretic activity, propensity to adsorption and acute toxicity. J Chem Pharm Res. 2014;6(5):1117-21.
18. Knysh Y, Panasenko O, Safonov A, inventors. Sodium 2-((4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazol-3-yl)thio)acetate, which shows actoprotective activity: patent 112619. Ukraine patent 18/2016. 2016.
19. Nair AB, Jacob S. A simple practice guide for dose conversion between animals and human. J Basic Clin Pharma. 2016;7(2):27-31. https://doi.org/10.4103/0976-0105.177703
20. Guide for the Care and Use of Laboratory Animals. Washington, D.C.: National Academies Press, 2011. https://doi.org/10.17226/12910
21. Union E. Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes. Strasbourg:Official Journal of the European Union. 2010;276:33-79. Available from: https://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2010:276:0033:0079:en:PDF .
22. Mironov AK. Guidelines for conducting preclinical studies of drugs. Part one. Moscow: Grif-K; 2012. p. 944.
23. Makarenko OL, Koptev MM, Filenko BM, Vynnyk NI, Kokovsʹka OV. The cervical fold suspension model of acute stress in rats and its impact on the spleen. Ukraïnsʹkij Žurnal Med Bìologìï Ta Sport. 2021;6:108-13. https://doi.org/10.26693/jmbs06.03.108
24. Ilderbayev OZ, Zharmakhanova GM, Okassova AK, Nursafina AZ, Ilderbayeva GO. Comparison of the performance of lipoperoxidation-antioxidant protection system in rats at different periods under immobilization stress effects. Med J Islam Repub Iran. 2021;35 (1):859-64 https://doi.org/10.47176/mjiri.35.113
25. Vorhees CV, Williams MT. Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nature Protocols. 2006;1(2):848-58. https://doi.org/10.1038/nprot.2006.116
26. Ammerlaan W, Trezzi JP, Lescuyer P, Mathay C, Hiller K, Betsou F. Method validation for preparing serum and plasma samples from human blood for downstream proteomic, metabolomic, and circulating nucleic acid-based applications. Biopreserv Biobank. 2014;12(4):269-80. https://doi.org/10.1089/bio.2014.0003
27. Situnayake RD, Crump BJ, Zezulka AV, Davis M, McConkey B, Thurnham DI. Measurement of conjugated diene lipids by derivative spectroscopy in heptane extracts of plasma. Annals of Clinical Biochemistry. 1990;27(3):258-66. https://doi.org/10.1177/000456329002700313
28. Esterbauer H, Cheeseman KH. Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. Methods in Enzymology. 1990;186:407-21. https://doi.org/10.1016/0076-6879(90)86134-H
29. Safonov A, Demianenko D, Vashchyk Y, Larianovska Y, Lytkin D, Shcherbyna R, et al. Histological study of a corrective influence of sodium 2-((4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazol-3-yl)thio) acetate on the state of rats liver under conditions of acute immobilization stress. Ankara Ecz Fak Derg. 2022;46(2):330-41. https://doi.org/10.33483/jfpau.1012893

Study Of The Stress-Protective Effect Of Sodium 2-((4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazol-3-yl)thio)acetate