A study of actoprotective activity of new 3-(thiophen-2-ylmethyl)-1H-1,2,4-triazole-5-thiol derivatives
DOI:
https://doi.org/10.14739/2409-2932.2020.3.216211Keywords:
triazoles, actoprotective activity, salts, heterocyclic compoundsAbstract
The issue of fatigue is quite topical for the modern humanity. In order to work harder and earn as much money as possible, a person takes various stimulants, which have a number of side effects. This problem is especially serioous in Asian countries.
To prevent such complications, scientists are trying to invent actoprotectors that would have minimal side effects.
1,2,4-triazole derivatives have proven themselves well as new substances with different spectrum of pharmacological activity.
The aim of this work is the investigation of actoprotective activity of new 3-(thiophen-2-ylmethyl)-1H-1,2,4-triazole-5-thiol derivatives.
Materials and methods. To study the actoprotective activity of new 3-(thiophen-2-ylmethyl)-1H-1,2,4-triazole-5-thiol derivatives, a group of 7 white nonlinear rats weighing 200–260 g was used.
Pharmacological activity was studied with the method of forced swimming. The study compounds, as well as the reference standard – Riboxin® (manufactured by Kyiv Vitamin Plant) was administered orally 20 minutes prior to the immersion of animals at a dose of 100 mg/kg. For comparison, we also used a control group of animals that received saline 20 minutes prior to the immersion.
Gravimetric measurements were performed on laboratory electronic analytical scales model ESJ-200-4(US).
Statistical results were calculated using Kolmogorov–Smirnov test and Shapiro–Wilk test.
Results. As a result, the actoprotective activity of 22 new compounds was investigated.
Compounds Ia, IIb, IIh have been found to have an actoprotective effect. Compound Ia surpasses the comparison drug.
The most active substance among the first synthesized salts is the potassium 2-((3-(thiophen-2-ylmethyl)-1H-1,2,4-triazol-5-yl)thio)acetate, which surpasses the comparison drug riboxin by 6.32 %.
Conclusions. Some conclusions are drawn regarding "structure - actoprotective effect" dependence: replacement of potassium cation by sodium cation leads to a decrease in biological activity; introduction of 4-chlorobenzylidene or 2,3-dimethoxybenzylidene substituent into the molecule of 2-((3-(thiophen-2-ylmethyl)-1H-1,2,4-triazol-5-yl)thio)acetohydrazide does not affect the actoprotective effect; introduction of benzylidene substituent, 3-nitrobenzylidene, 4-dimethylaminobenzylidene, 2,4-dimethylbenzylidene into the molecule of 2-((3-(thiophen-2-ylmethyl)-1H-1,2,4-triazol-5-yl)thio)acetohydrazide negatively affects the fatigue in rats.
References
El-Wahab, H., Hamdy,A.-R. M., Gamal-Eldin, S. A., & El-Gendy, M. A. (2011). Synthesis, biological evaluation and molecular modeling study of substituted 1,2,4-triazole-3-acetic acid derivatives. Der Pharma Chemica, 3(6), 540-552.
Kaplaushenko, A. H., Sameliuk, Yu. H., & Kucheriavyi, Yu. M. (2016). Praktychne znachennia ta zastosuvannia pokhidnykh 1,2,4-triazolu [Practical value and application of derivatives of 1,2,4-triazole]. Zaporizhzhia. [in Ukrainian].
Hulina, Yu. S., & Kaplaushenko, А. G. (2018). Synthesis, physical and chemical properties of 5-((1Н-tetrazole-1-yl)methyl)-4-R-4Н-1,2,4-triazole-3-thiols and their chemical transformations. Russian Journal of Biopharmaceuticals, 10(1), 26-30.
Rud, A. M., Kaplaushenko, A. G., & Yurchenko, I. O. (2018). Synthesis, physical and chemical properties of 2-((5-(hydroxy(phenyl)methyl)-4R-4H-1,2,4-triazole3-yl)thio)acetic acids and its salts. Zaporozhye medical journal, 20(1), 105-109. https://doi.org/10.14739/2310-1210.2018.1.122126
Wu, J. W., Yin, L., Liu, Y. Q., Zhang, H., Xie, Y. F., Wang, R. L., & Zhao, G. L. (2019). Synthesis, biological evaluation and 3D-QSAR studies of 1,2,4-triazole-5-substituted carboxylic acid bioisosteres as uric acid transporter 1 (URAT1) inhibitors for the treatment of hyperuricemia associated with gout. Bioorganic and Medicinal Chemistry Letters, 29(3), 383-388. https://doi.org/10.1016/j.bmcl.2018.12.036
Hassan, A. A., Mohamed, N. K., Aly, A. A., Bräse, S., & Nieger, M. (2019). Eschenmoser-Coupling Reaction Furnishes Diazenyl-1,2,4-triazole-5(4H)-thione Derivatives. ChemistrySelect, 4(2), 465-468. https://doi.org/10.1002/slct.201802870
Moreno-Fuquen, R., Arango-Daraviña, K., Becerra, D., Castillo, J. C., Kennedy, A. R., & Macías, M. A. (2019). Catalyst– and solvent-free synthesis of 2-fluoro-N-(3-methylsulfanyl-1H-1,2,4-triazol-5-yl)benzamide through a microwave-assisted fries rearrangement: X-ray structural and theoretical studies. Acta crystallographica. Section C, Structural chemistry, 75(Pt 3), 359-371. https://doi.org/10.1107/S2053229619002572
Hulina, Yu. S., & Kaplaushenko, A. G. (2016). Syntez i fizyko-khimichni vlastyvosti 2-(5-(1H-tetrazol-1-ilmetyl)-4-R-4H-1,2,4-triazol-3-iltio)-atsetatnykh(propanovykh), 2-, 4-(5-(1H-tetrazol-1-ilmetyl)-4-fenil-4H-1,2,4-triazol-3-iltiometyl)-benzoinykh kyslot ta yikh solei [Synthesis and physical-chemical properties of 2-(5-(1Н-tetrazol-1-ylmethyl)-4-R-4Н-1,2,4-triazol-3-yltio)-acetic (propanoic), 2-, 4-(5-(1Н-tetrazol-1-ylmethyl)-4-phenyl-4Н-1,2,4-triazol-3-yltiometil)-benzoic acids and their salts]. Current issues in pharmacy and medicine: science and practice, 2, 32-37. [in Ukrainian]. https://doi.org/10.14739/2409-2932.2016.2.71115
Tang, Y., Yu, F., Huang L., & Hu, Z. (2019). The changes of antifungal susceptibilities caused by the phenotypic switching of Candida species in 229 patients with vulvovaginal candidiasis. Journal of Clinical Laboratory Analysis, 33(1), e22644. https://doi.org/10.1002/jcla.22644
Pillai, R., Karrouchi, K., Fettach, S., Armaković, S., Armakovic, S., Brik, Y., Taoufik, J., Radi, S., Faouzi, M. E., & Ansar, M. (2019). Synthesis, spectroscopic characterization, reactive properties by DFT calculations, molecular dynamics simulations and biological evaluation of Schiff bases tethered 1,2,4-triazole and pyrazole rings. Journal of Molecular Structure, 1177, 47-54. https://doi.org/10.1016/j.molstruc.2018.09.037
Shcherbyna, R. O., Panasenko, O. I., Knysh, Ye. H., & Varynskyy, B. О. (2014). Syntez i fizyko-khimichni vlastyvosti 2-((4-R-3-(morfolinometylen)-4H-1,2,4-triazol-5-il)tio) atsetatnykh kyslot [Synthesis and physical-chemical properties of 2-((4-R-3-(morpholinomethylen)-4H-1,2,4-triazole-5yl)thio)acetic acid]. Current Issues in Pharmacy and Medicine: Science and Practice, (3), 18-21. [in Ukrainian]. https://doi.org/10.14739/2409-2932.2014.3.30016
Stefanov, O. V. (Ed.). (2001). Doklinichni doslidzhennia likarskykh zasobiv [Preclinical research of medicinal products]. Kyiv: Avitsena.
Downloads
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access)
