Antimicrobial and antifungal activity of new 4-(5-((5-(alkylthio)-4-R-4H-1,2,4-triazole-3-yl)thio)-1H-1,2,4-triazole-3-yl)pyridines

Authors

DOI:

https://doi.org/10.14739/2409-2932.2020.3.216204

Keywords:

1, 2, 4-triazole, antimicrobial activity, antifungal activity

Abstract

 

The resistance of such strains as Staphylococcus aureus, Escherichia coli extends to many antimicrobial drugs. This problem can be solved by searching for new drugs with high bactericidal and antifungal action. Recent studies have shown the promise of searching for biologically active substances of antimicrobial and antifungal action among 1,2,4-triazole derivatives.

The aim of this work was to develop the antimicrobial and antifungal effects of the homologous series of S-alkyl-substituted 4-R-5-(((3-(pyridin-4-yl)-1H-1,2,4-triazole-5-yl)thio)methyl)-4Н-1,2,4-triazole-3-thiols and draw conclusions regarding the structural and functional relationship of the synthesized compounds.

Materials and methods. The subject of research was 4-(5-(((5-(alkylthio)-4-methyl-4H-1,2,4-triazole-3-yl)thio)-1H-1,2,4-triazole-3-yl)pyridines and 4-(5-(((5-(alkylthio)-4-ethyl-4H-1,2,4-triazole-3-yl)thio)-1H-1,2,4-triazole-3-yl)pyridines. The activity was analyzed by the method of two-fold serial dilutions on test cultures of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Candida albicans.

The results of the biological screening showed that all tested compounds exhibited antibacterial action (MIC – in the range of 31.25–62.50 μg/ml, MBС – in the range of 62.5–125.0 μg/ml) and antifungal effect (MIC – in within 31.25–62.50 μg/ml, MFС – within 62.5–125.0 μg/ml) relative to the control. The obtained compounds exhibit more pronounced activity against the Pseudomonas aeruginosa strain (MIC – in the range of 31.25–62.50 μg/ml, MBcС – in the range of 62.5–125.0 μg/ml) and antifungal activity against the Candida albicans strain (MIC – within 31.25–62.50 μg/ml, MFС – within 62.5–125.0 μg/ml) relative to the control.

Conclusions. The biological screening data indicate that the search among the given bis-1,2,4-triazole derivatives is promising. The most active among the series of S-alkyl-substituted 4-R-5-(((3-(pyridin-4-yl)-1Н-1,2,4-triazole-5-yl)thio)methyl)-4Н-1,2,4-triazole-3-thiols was compound 4-(5-(((4-methyl-5-(pentylthio)-4H-1,2,4-triazole-3-yl)thio)-1H-1,2,4-triazole-3-yl)pyridine, which exhibited the most pronounced antimicrobial effect against the Staphylococcus aureus strain (MIC – 15.6 μg/ml, MBС – 31.25 μg/ml) indicate the prospects of searching in the specified number of substituted.

References

Vashchyk, Y., Shcherbyna, R., Parchenko, V., Bushueva, i., Gutyj, B., Fotina, H., Fotina, T., & Stronskyi, Y. (2020). Histological study of a corrective influence of a compound potassium 2-((4-amino-5-(morpholinomethyl)-4h-1,2,4-triazol-3-yl)thio)acetate (PKR-173) on the state of chicken's liver under infection by Pseudomonas Aeruginosa. Ankara Universitesi Eczacilik Fakultesi Dergisi, 44(1), 1-17. https://doi.org/10.33483/jfpau.567757

Datoussaid, Y., Othman, A., & Kirsch, G. (2012). Synthesis and antibacterial activity of some 5,5'-(1,4-phenylene)-bis-1,3,4-oxadiazole and bis-1,2,4-triazole derivatives as precursors of new S-nucleosides. South African journal of chemistry, 65, 30-35.

Bigdan, O. A., Parchenko, V. V., Kyrychko, B. P., Zvenigorodska, T. V., Gutyj, B. V., Gunchak, A. V., Slivinska, L. G., Savchuk, L. B., Nazaruk, N. V., Kit, L. P., Dashkovskyy, O. O., & Guta, Z. A. (2020). Test of antimicrobial activity of morpholine 2- (5- (3-fluorophenyl) -4-amino-1,2,4-triazol-3-ilthio) acetate (BKP-115) by experimental model of pancreatitis in rats. Ukrainian Journal of Ecology, 10(3), 201-207.

Chaudhary, P. M., Tupe, S. G., Jorwekar, S. U., Sant, D. G., Deshpande, S. R., Maybhate, S. P., Likhite, A.P., Deshpande, M. V. (2015). Synthesis and antifungal potential of 1,2,3-triazole and 1,2,4-triazole thiol substituted strobilurin derivatives. Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 54B(7), 908-917.

Aher, N. G., Pore, V. S., Mishra, N., Kumar, A., Shukla, P., Sharma, A., & Bhat, M. K. (2009). Synthesis and antifungal activity of 1,2,3-triazole containing fluconazole analogues. Bioorganic & medicinal chemistry letters, 19(3), 759-763. https://doi.org/10.1016/j.bmcl.2008.12.026

Shcherbyna, R. (2019). Microwave-assisted synthesis of some new derivatives of 4-substituted-3-(morpholinomethyl)-4H-1,2,4-triazole-5-thioles. Ankara Universitesi Eczacilik Fakultesi Dergisi, 43(3), 220-229. https://doi.org/10.33483/jfpau.533166

Gilani, S. J., Khan, S. A., & Siddiqui, N. (2010). Synthesis and pharmacological evaluation of condensed heterocyclic 6-substituted 1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazole and 1,3,4-oxadiazole derivatives of isoniazid. Bioorganic and Medicinal Chemistry Letters, 20(16), 4762-4765. https://doi.org/10.1016/j.bmcl.2010.06.125

Rao, D. N., Prasad, A. R., Spoorthy, Y. N., Rao, D. R., & Ravindranath, L. K. (2015). Synthesis, Characterization and Antimicrobial Evaluation of Substituted 1,2,4-Triazole Thiones Containing Pyrazole Moiety. Journal of Clinical and Analytical Medicine, 6(5). https://doi.org/10.4328/ jcam.2323

Volianskyi, Yu. L., Hrytsenko, I. S., Shyrobokov, V. P., Biriukova, S. V., & Palii, V. H. (2004). Vyvchennia spetsyfichnoi aktyvnosti protymikrobnykh likarskykh zasobiv [Specific activity detection of antimicrobial medicines: Guidelines]. Kyiv. [in Ukrainian].

How to Cite

1.
Karpun YO, Polishchuk NM. Antimicrobial and antifungal activity of new 4-(5-((5-(alkylthio)-4-R-4H-1,2,4-triazole-3-yl)thio)-1H-1,2,4-triazole-3-yl)pyridines. Current issues in pharmacy and medicine: science and practice [Internet]. 2020Nov.16 [cited 2024Oct.6];13(3). Available from: http://pharmed.zsmu.edu.ua/article/view/216204

Issue

Section

Original research