Synthesis and properties of S-alkyl 4-amino-5-(5-(3-fluorophenyl)-pyrazol-3-yl)-1,2,4-triazole-3-thiol derivatives

Authors

DOI:

https://doi.org/10.14739/2409-2932.2023.1.273461

Keywords:

1,2,4-triazole, properties, computer simulation, pyrazole

Abstract

An important direction of modern pharmaceutical science is the creation of promising biologically active compounds, which in the hands of scientists can be transformed into effective medicinal products. Heterocyclic compounds are the undisputed leader in solving this problem. A well-known fact and a well-founded approach to achieving the desired pharmacological effect is the combination of different heterocyclic fragments in the structure of one molecule. And here it makes sense to focus our attention on such heterocycles as pyrazole and 1,2,4-triazole. After all, a number of well-known medicines have already been invented on their basis. Thus, the construction of a chemical tandem with heterocyclic blocks of the specified nature is an actual and promising direction of scientific work.

The aim of the work was to create a number of S-alkyl derivatives of 4-amino-5-(5-(3-fluorophenyl)pyrazol-3-yl)-1,2,4-triazole-3-thiol and study their properties, as well as preliminary selective establishment biological potential of these compounds.

Materials and methods. The synthesis of the target products of chemical transformation was successfully implemented by the step-by-step use of well-known methods of organic synthesis. Thus, the first stage was successfully implemented with the help of available reagents, the role of which was performed by diethyl oxalate and 1-(3-fluorophenyl)ethan-1-one with the participation of sodium methylate. The next stage involved hydrazinolysis. Subsequently, the corresponding potassium xanthogenate was successfully synthesized, which was subsequently transformed under the action of hydrazine hydrate into the target 4-amino-5-(5-(3-fluorophenyl)pyrazol-3-yl)-1,2,4-triazole-3-thiol. The next stage was S-alkylation. The structure of all synthesized substances was determined with IR spectrophotometry, 1H NMR spectroscopy, and elemental analysis. The individuality of the compounds was confirmed by high-performance liquid chromatography-mass spectrometry. In silico studies were carried out with well-known software products, namely: AutoDock Vina, Biovia Discovery Studio, Hyper Chem 7.5, and Open Babel. Cyclooxygenase-2, lanosterol 14α-demethylase, and anaplastic lymphoma kinase were used as model enzymes.

Results. The optimal conditions for the stepwise creation of S-alkyl derivatives of 4-amino-5-(5-(3-fluorophenyl)pyrazol-3-yl)-1,2,4-triazole-3-thiol were established and the preparation of the specified compounds was carried out. The use of molecular docking made it possible to determine the perspective of further research on anti-inflammatory, antifungal, and antitumor properties in a number of synthesized structures.

Conclusions. S-alkyl derivatives of 4-amino-5-(5-(3-fluorophenyl)pyrazol-3-yl)-1,2,4-triazole-3-thiol are reasonably promising objects for the study of antifungal activity.

Author Biographies

S. O. Fedotov, Zaporizhzhia State Medical University, Ukraine

PhD-student of the Department of Natural Sciences for Foreign Students and Toxicological Chemistry

A. S. Hotsulia, Zaporizhzhia State Medical University, Ukraine

PhD, DSc, Associate Professor of the Department of Natural Sciences for Foreign Students and Toxicological Chemistry

References

Othman, A. A., Kihel, M., & Amara, S. (2019). 1,3,4-Oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole derivatives as potential antibacterial agents. Arabian Journal of Chemistry, 12(7), 1660-1675. https://doi.org/10.1016/ j.arabjc.2014.09.003

Shcherbyna, R., Panasenko, O., Polonets, O., Nedorezanıuk, N., & Duchenko, M. (2021). Synthesis, antimicrobial and antifungal activity of ylidenhydrazides of 2-((4-R-5-R1-4Н-1,2,4-triazol-3-yl)thio)acetaldehydes. Ankara Universitesi Eczacilik Fakultesi Dergisi, 45(3), 504-514. https://doi.org/10.33483/jfpau.939418

Frolova, Y., Kaplaushenko, A., & Nagornaya, N. (2020). Design, synthesis, antimicrobial and antifungal activities of new 1,2,4-triazole derivatives containing 1H-tetrazole moiety. Ankara Universitesi Eczacilik Fakultesi Dergisi, 44(1), 70-88. https://doi.org/10.33483/jfpau.574001

Samelyuk, Y. G., & Kaplaushenko, A. G. (2014). Synthesis of 3-alkylthio(sulfo)-1,2,4-triazoles, containing methoxyphenyl substituents at C5atoms, their antipyretic activity, propensity to adsorption and acute toxicity. Journal of Chemical and Pharmaceutical Research, 6(5), 1117-1121.

Gotsulya, A., Zaika, Y., & Brytanova, T. (2022). Synthesis, properties and biological potential some condensed derivatives 1,2,4-triazole. Ankara Universitesi Eczacilik Fakultesi Dergisi, 46(2), 308-321. https://doi.org/10.33483/jfpau.971602

Ismail, M. I., Mohamady, S., Samir, N., & Abouzid, K. A. M. (2020). Design, Synthesis, and Biological Evaluation of Novel 7H-[1,2,4]Triazolo[3,4-b][1,3,4]thiadiazine Inhibitors as Antitumor Agents. ACS omega, 5(32), 20170-20186. https://doi.org/10.1021/acsomega.0c01829

Boraei, A. T. A., Ghabbour, H. A., Gomaa, M. S., El Ashry, E. S. H., & Barakat, A. (2019). Synthesis and Anti-Proliferative Assessment of Triazolo-Thiadiazepine and Triazolo-Thiadiazine Scaffolds. Molecules (Basel, Switzerland), 24(24), 4471. https://doi.org/10.3390/molecules24244471

Sonawane, R. K., & Mohite, S. K. (2021). Heterocyclic Bridgehead Nitrogen Atom System: Review on [1,2,4] Triazolo[3,4-b] [1,3,4] thiadiazole and Its Pharmacological Screening. Asian Journal of Research in Chemistry, 217-220. https://doi.org/10.52711/0974-4150.2021.00038

Charitos, G., Trafalis, D. T., Dalezis, P., Potamitis, C., Sarli, V., Zoumpoulakis, P., & Camoutsis, C. (2019). Synthesis and anticancer activity of novel 3,6-disubstituted 1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazole derivatives. Arabian Journal of Chemistry, 12(8), 4784-4794. https://doi.org/10.1016/j.arabjc.2016.09.015

Šermukšnytė, A., Kantminienė, K., Jonuškienė, I., Tumosienė, I., & Petrikaitė, V. (2022). The Effect of 1,2,4-Triazole-3-thiol Derivatives Bearing Hydrazone Moiety on Cancer Cell Migration and Growth of Melanoma, Breast, and Pancreatic Cancer Spheroids. Pharmaceuticals, 15(8), 1026. https://doi.org/10.3390/ph15081026

Grytsai, O., Valiashko, O., Penco-Campillo, M., Dufies, M., Hagege, A., Demange, L., Martial, S., Pagès, G., Ronco, C., & Benhida, R. (2020). Synthesis and biological evaluation of 3-amino-1,2,4-triazole derivatives as potential anticancer compounds. Bioorganic chemistry, 104, 104271. https://doi.org/10.1016/j.bioorg.2020.104271

Safonov, A. A. (2020). Method of synthesis novel N’-Substituted- 2-((5-(Thiophen-2-Ylmethyl)-4H-1,2,4-Triazol-3-YL)Thio) acetohydrazides. Ankara Universitesi Eczacilik Fakultesi Dergisi, 44(2), 242-252. https://doi.org/10.33483/jfpau.580011

Karpenko, Y., Hunchak, Y., Gutyj, B., Hunchak, A., Parchenko, M., & Parchenko, V. (2022). Advanced research for physico-chemical properties and parameters of toxicity piperazinium 2-((5-(furan-2-yl)-4-phenyl-4H-1,2,4-triazol-3-yl)thio)acetate. ScienceRise: Pharmaceutical Science, 2(36), 18-25. https://doi.org/10.15587/2519-4852.2022.255848

Gotsulya, A. S. (2020). 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 Universitesi Eczacilik Fakultesi Dergisi, 44(2), 211-219. https://doi.org/10.33483/jfpau.616116

Fedotov, S. O., & Hotsulia, А. 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. https://doi.org/10.14739/2409-2932.2021.3.243176

Biovia. (2019). Discovery Studio Visualizer, v 19.1.0.18287 [Software]. Retrieved from https://www.3dsbiovia.com/

ChemAxon. (2015). MarvinSketch, Version 6.3.0. [Software]. Retrieved from https://www.chemaxon.com

Worldwide Protein Data Bank. (n.d.). Protein Data Bank (PDB) [Database]. Retrieved from http://www.pdb.org

Downloads

Published

2023-03-10

How to Cite

1.
Fedotov SO, Hotsulia AS. 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 [Internet]. 2023Mar.10 [cited 2024May24];16(1):5-11. Available from: http://pharmed.zsmu.edu.ua/article/view/273461

Issue

Section

Original research