In silico study of properties in the series of 1-alkyl-4-(((5-nitrofuran-2-yl)methylene)amino)- 1,2,4-triazole halides




1,2,4-triazole, design, ADME analysis, molecular modeling


1,2,4-Triazole derivatives open up wide horizons for modern medicinal chemists to develop innovative drugs. The use of 1,2,4-triazole derivatives in pharmacological research is based on their ability to produce an effective effect on biological systems and interact with molecular targets. These azoles can be used to regulate various physiological processes, which opens up the possibility of their effective use in the treatment of various diseases.

Targeted modification of the structure of 1,2,4-triazole derivatives opens up wide opportunities for the creation of biologically active compounds with improved properties, which contributes to further advances in pharmaceutical research and the development of new, effective drugs.

The aim of this work is to predictively assess the pharmacological potential of 1-alkyl-4-(((5-nitrofuran-2-yl)methylene)amino)-1,2,4-triazole halides by in silico studies.

Materials and methods. ADME-analysis is a method of studying the physical-chemical and pharmacokinetic parameters of the studied substances using the online resource SwissADME. Molecular docking is a method of predicting and evaluating the interaction between a ligand molecule and the three-dimensional structure of the target protein. The ligands have been prepared with the software MarvinSketch 6.3.0, Hyper Chem 8, and AutoDockTools-1.5.6, whereas the software packages Discovery Studio 4.0 and AutoDockTools-1.5.6 have been used for the preparation of enzymes. The Vina program was used for direct molecular docking.

Results. A prescreening analysis was conducted on a virtual series of 1-alkyl-4-(((5-nitrofuran-2-yl)methylene)amino)-1,2,4-triazole halides, recognized as potential sources of biologically active substances. The study involved determining the main physicochemical characteristics and unveiling general pharmacokinetic parameters of the molecules. The Vina program was employed to identify the nature and number of amino acid residues in the active sites of model enzymes interacting with the proposed ligands. Results indicate the highest affinity for lanosterol 14α-demethylase. However, the analysis of ligand complexes with cyclooxygenase-2 and anaplastic lymphoma kinase suggests a low probability of a significant effect on these enzymes.

Conclusions. The overall prognosis for bioavailability in the case of oral administration of dosage forms with the investigated substances is favorable. Pharmacodynamics in silico studies allow us to identify 1-heptyl- and 1-octyl-4-(((5-nitrofuran-2-yl)methylene)amino)-1,2,4-triazolium bromides as potential antifungal agents that can reasonably be involved in further in-depth studies of this type of activity.

Author Biographies

L. I. Kucherenko, Zaporizhzhia State Medical and Pharmaceutical University, Ukraine

PhD, DSc, Professor, Head of the Department of Pharmaceutical, Organic and Bioorganic Chemistry

T. S. Brytanova, Zaporizhzhia State Medical and Pharmaceutical University, Ukraine

PhD, Senior Lecturer of the Department of Pharmaceutical, Organic and Bioorganic Chemistry

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

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


Ahmad S, Alam O, Naim MJ, Shaquiquzzaman M, Alam MM, Iqbal M. Pyrrole: an insight into recent pharmacological advances with structure activity relationship. Eur J Med Chem. 2018;527-61. doi:

Afsarian MH, Farjam M, Zarenezhad E, Behrouz S, Rad MN. Synthesis, antifungal evaluation and molecular docking studies of some tetrazole derivatives. Acta Chim Slov. 2019;66(4):874-87. doi:

Zarenezhad E, Farjam M, Iraji A. Synthesis and biological activity of pyrimidines-containing hybrids: focusing on pharmacological application. J Mol Struct. 2021;1230. doi:

Martínez-Matías N, Rodríguez-Medina JR. Fundamental concepts of azole compounds and triazole antifungals: a beginner’s review. P R Health Sci J. 2018;37(3):135-42.

Shcherbyna R, Panasenko O, Polonets O, Nedorezaniuk N, Duchenko M. 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. 2021;45(3):504-14. doi:

Samelyuk YG, Kaplaushenko AG. Synthesis of 3-alkylthio(sulfo)-1,2,4-triazoles, containing methoxyphenyl substituents at c5atoms atoms, their antipyretic activity, propensity to adsorption and acute toxicity. J Chem Pharm Res. 2014;6(5):1117-21.

Gotsulya A, Zaika Y, Brytanova T. Synthesis, properties and biological potential some condensed derivatives 1,2,4-triazole. Ankara Universitesi Eczacilik Fakultesi Dergisi. 2022;46(2):308-21. doi:

Malani AH, Makwana AH, Makwana HR. A brief review article: Various synthesis and therapeutic importance of 1, 2, 4-triazole and its derivatives. Mor. J. Chem. 2017;5(1):41-58.

Bekircan O, Menteşe E, Ülker S, Kucuk C. Synthesis of some new 1,2,4-triazole derivatives starting from 3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol with anti-lipase and anti-urease activities. Arch Pharm. 2014;347(6):387-97. doi:

Šermukšnytė A, Kantminienė K, Jonuškienė I, Tumosienė I, Petrikaitė V. 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. 2022;15(8):1026. doi:

Grytsai O, Valiashko O, Penco-Campillo M, Dufies M, Hagege A, Demange L, et al. Synthesis and biological evaluation of 3-amino-1,2,4-triazole derivatives as potential anticancer compounds. Bioorg Chem. 2020;104:104271. doi:

Safonov AA. 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. 2020;44(2):242-52. doi:

Karpenko Y, Hunchak Y, Gutyj B, Hunchak A, Parchenko M, Parchenko V. 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. 2022;2(36):18-25. doi:

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 Universitesi Eczacilik Fakultesi Dergisi. 2020;44(2):211-9. doi:

Fedotov SO, Hotsulia АS. 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. 2021;14(3):268-74. doi:

Chekman IS, Nebesna TY, Symonov PV. In silico: novyi napriam v rozrobtsi farmakolohichnykh ta farmatsevtychnykh vlastyvostei likarskykh zasobiv [In silico: a new direction in the development of pharmacological and pharmaceutical properties of medicines]. Klinichna farmatsiia. 2012;16(2):4-14. Ukrainian.

Discovery Studio Visualizer v19.1.018287. Accelrys Software Inc., [Internet]; [сited 2024 Jan 11]. Available from:

MarvinSketch version 20.20.0, ChemAxon. [Internet]. Available from:

Protein Data Bank. [Internet]; [сited 2024 Jan 11]. Available from:



How to Cite

Kucherenko LI, Brytanova TS, Hotsulia AS. In silico study of properties in the series of 1-alkyl-4-(((5-nitrofuran-2-yl)methylene)amino)- 1,2,4-triazole halides. Current issues in pharmacy and medicine: science and practice [Internet]. 2024Feb.23 [cited 2024Jun.21];17(1):10-6. Available from: