Synthesis, antimicrobial and antifungal activity of 3-(2-bromophenyl)-5-(alkylthio)-4-phenyl-4H-1,2,4-triazoles




organic synthesis, antimicrobial activity, antifungal activity, 1,2,4-triazole, heterocyclic compounds


To select a molecule that could become a promising pharmacological agent, chemists use already-known heterocyclic bases by adding pharmacologically active groups. One such heterocyclic system is 1,2,4-triazole base, on the basis of which a huge number of biologically active compounds have already been found. It is known that 1,2,4-triazole derivatives show a fairly high antimicrobial and antifungal effect while remaining low-toxic compounds and 5-alkylthio-1,2,4-triazoles exhibit antimicrobial and antifungal activity. Based on the literature search, it can be concluded that 3-(2-bromophenyl)-5-(alkylthio)-4-phenyl-4H-1,2,4-triazoles are insufficiently studied.

The aim of the work was to synthesize and investigate antimicrobial and antifungal activity among 3-(2-bromophenyl)-5-(alkylthio)-4-phenyl-4H-1,2,4-triazoles.

Materials and methods. It was used 5-(2-bromophenyl)-4-phenyl-4H-1,2,4-triazole-3-thiol as a starting substance, which was synthesized by previously described techniques. 3-(2-Bromophenyl)-5-(alkylthio)-4-phenyl-4H-1,2,4-triazoles were obtained by alkylation of the starting thiol with halohenalkanes (according to the first method) and the addition of hydrochloric acid in an alcoholic medium, then subsequent heating in microwave synthesis system (by the second method). To study the antimicrobial and antifungal activity of the newly synthesized 3-(2-bromophenyl)-5-(alkylthio)-4-phenyl-4H-1,2,4-triazoles, the method of serial dilutions was used according to guidelines.

Results. 3-(2-Bromophenyl)-5-(alkylthio)-4-phenyl-4H-1,2,4-triazoles were obtained by two methods: a) an equivalent amount of halohenalkane was added to 5-(2-bromophenyl)-4-phenyl-4H-1,2,4-triazole-3-thiol (I) (solvent – KOH pre-dissolved in 2-propanol). Boiled to pH = 7; b) 5-(2-bromophenyl)-4-phenyl-4H-1,2,4-triazole-3-thiol (I) (solvent – methyl or 1-propyl alcohol and 10 drops of HCl) was heated in Milestone Flexi Wave microwave synthesis system. Reaction conditions: The mixture was heated for 45 minutes at a temperature of 150 °C, a pressure 14.4 bar, ΔMW ≈ 200 W. The completeness of the reaction was determined using a gas chromatograph Agilent 7890B with a mass spectrometric detector 5977B. Antimicrobial and antifungal activity of 3-(2-bromophenyl)-5-(alkylthio)-4-phenyl-4H-1,2,4-triazoles (6 new compounds) was investigated. The most active compound with antifungal and antimicrobial effect was IIi. Substances IIa–IIe had moderate antimicrobial effect.

Conclusions. New 3-(2-bromophenyl)-5-(alkylthio)-4-phenyl-4H-1,2,4-triazoles were synthesized by two methods. The antimicrobial and antifungal activity was investigated for the obtained compounds. The most active compound was 3-(2-bromophenyl)-5-(decylthio)-4-phenyl-4H-1,2,4-triazole (IIi). Some conclusions were drawn regarding the dependence of “structure – antimicrobial and antifungal effect”: the antimicrobial effect increased with the length of the carbon radical; changing the decyl radical to another one in the molecule 3-(2-bromophenyl)-5-(alkylthio)-4-phenyl-4H-1,2,4-triazole reduced antifungal activity.

Author Biographies

A. A. Safonov, Zaporizhzhia State Medical University, Ukraine

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

O. I. Panasenko, Zaporizhzhia State Medical University, Ukraine

Dr. hab., Professor, Head of the Department of Natural Sciences for Foreign Students and Toxicological Chemistry


Kaplaushenko, A. G. (2013). Doslidzhennia zi stvorennia novoho oryhinalnoho vitchyznianoho likarskoho zasobu na osnovi 1,2,4-triazolu [The Research of Creating a New Original Domestic Drug Based on 1,2,4-triazole]. Naukovyi zhurnal MOZ Ukrainy, (2), 115-121. [in Ukrainian].

Shcherbyna, R. O. (2014). Analiz farmakolohichnoi aktyvnosti pokhidnykh 1,2,4-triazolu [Analysis of pharmacological activity of 1,2,4-triazole derivatives]. Farmatsevtychnyi chasopys, (4), 145-150. [in Ukrainian].

Li, Y. S., Tian, H., Zhao, D. S., Hu, D. K., Liu, X. Y., Jin, H. W., Song, G. P., & Cui, Z. N. (2016). Synthesis and bioactivity of pyrazole and triazole derivatives as potential PDE4 inhibitors. Bioorganic & medicinal chemistry letters, 26(15), 3632-3635.

Shcherbyna, R. O., Panasenko, O. I., & Knysh, Ye. H. (2016). Vyvchennia antyoksydantnoi aktyvnosti solei 2-((4-R-3-(morfolinometylen)-4H1,2,4-tryazol-5-il)tio)atsetatnykh kyslot [The studying of antioxidant activity of salts 2-((4-R-3-(morpholinomethylen)-4H-1,2,4-triazole-5-yl) thio)acetic acids]. Ukrainian Biopharmaceutical Journal, (1), 37-40. [in Ukrainian].

Shcherbyna, R. O., Kapelyanovych, Ye. V., Pruhlo, Ye. S., Panasenko, O. I., & Knysh, Ye. H. (2014). Doslidzhennia aktoprotektornoi aktyvnosti pokhidnykh 4-R-3-(morfolinometylen)-1,2,4-triazol-5-tiolu [The studying of actoprotective action of 4-R-3-(morpholinomethylene)-1,2,4-triazole-5-thiole derivatives]. Odeskyi medychnyi zhurnal, (6), 19-22. [in Ukrainian].

Murty, M. S. R., Ram, K. R., Rao, R. V., Yadav, J. S., Rao, J. V., & Velatooru, L. R. (2012). Synthesis of new S-alkylated-3-mercapto-1,2,4-triazole derivatives bearing cyclic amine moiety as potent anticancer agents. Letters in Drug Design & Discovery, 9(3), 276-281.

Can, N. Ö., Acar Çevik, U., Sağlık, B. N., Levent, S., Korkut, B., Özkay, Y., & Koparal, A. S. (2017). Synthesis, Molecular Docking Studies, and Antifungal Activity Evaluation of New Benzimidazole-Triazoles as Potential Lanosterol 14α-Demethylase Inhibitors. Journal of Chemistry, 2017.

Singh, R., Kashaw, S., Mishra, V., Mishra, M., Rajoriya, V., & Kashaw, V. (2018). Design and synthesis of new bioactive 1,2,4-triazoles, potential antitubercular and antimicrobial agents. Indian journal of pharmaceutical sciences, 80(1), 36-45.

Samelyuk, Yu. H., & Kaplaushenko, A. H. (2015). Hostra toksychnist 5-(2-, 3-, 4-metoksyfenil, (3,4,5-trymetoksyfenil)-)-1,2,4-triazol-3-tioniv ta yikh tiopokhidnykh [Acute toxicity of 5-(2-, 3-, 4-methoxyphenyl, (3,4,5-trimethoxyphenyl)-)-1,2,4-triazole-3-thiones and their thioderivatives]. Current issues in pharmacy and medicine: science and practice, (3), 57-60. [in Ukrainian].

Suhak, O. A., Panasenko, O. I., Knysh, Ye. G., & Kamyshny, O. M. (2015). Protymikrobna ta protyhrybkova aktyvnist pokhidnykh 3-(alkiltio)-4-R-5-(tiofen-2-ilmetyl)-4H-1, 2, 4-triazoliv [Antibacterial and antifungal activity of derivatives 3-(alkylthio)-4-R-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole]. Current issues in pharmacy and medicine: science and practice, (3), 67-70. [in Ukrainian].

Safonov, A. A., & Nevmyvaka, A. V. (2020). Synthesis of novel 3-(2-bromophenyl)-4-substituted-1H-1,2,4-triazole5(4H)-thiones derivatives. Current issues in pharmacy and medicine: science and practice, 13(1), 11-16.

Volianskyi, Yu. L., Hrytsenko, I. S., Shyrobokov, V. P. et al. (2004). Vyvchennia spetsyfichnoi aktyvnosti protymikrobnykh likarskykh zasobiv [Study of the specific activity of antimicrobial drugs]. Derzhavnyi farmakolohichnyi tsentr. [in Ukrainian].




How to Cite

Safonov AA, Panasenko OI. Synthesis, antimicrobial and antifungal activity of 3-(2-bromophenyl)-5-(alkylthio)-4-phenyl-4H-1,2,4-triazoles. CIPM [Internet]. 2022Nov.15 [cited 2023Dec.8];15(3):235-40. Available from:



Original research