In silico study of potential bacterial peptide deformylase inhibitors among 4-((furan-2-ylmethyl)amino)-3,5-dimethyl-1-(2-aryl-2-oxoethyl)-1,2,4-triazolium bromides
DOI:
https://doi.org/10.14739/2409-2932.2026.1.342356Keywords:
1,2,4-triazole, peptide deformylase, in silico, docking, actinonin, antimicrobial activityAbstract
Heterocyclic compounds play a key role in the development of new biologically active substances, among which 1,2,4-triazole derivatives attract particular attention. The combination of this heterocyclic core with other heterocyclic pharmacophoric fragments within a single molecule is considered a promising strategy for the design of potential drug candidates.
The aim of this study was to evaluate the potential antimicrobial activity of 4-((furan-2-ylmethyl)amino)-3,5-dimethyl-1-(2-aryl-2-oxoethyl)-1,2,4-triazolium bromides using molecular docking to the peptide deformylase (PDF) of Escherichia coli and Staphylococcus aureus.
Materials and methods. The three-dimensional structures of the ligands were modeled using ChemSketch software, while the crystallographic structures of the peptide deformylase (PDF) enzyme were obtained from the Protein Data Bank: the Escherichia coli isoform (EcPDF, PDB ID: 1BSK) and the Staphylococcus aureus isoform (SaPDF, PDB ID: 1LQW) were used. Molecular docking was performed using AutoDock Vina, and the types of intermolecular interactions were analyzed with Discovery Studio Visualizer. The minimum binding energy (Emin), reflecting the stability of the “ligand – enzyme” complex, was used as an indicator of binding efficiency.
Results. Nitro-substituted compounds exhibited the highest affinity towards the active sites of both enzymes. In particular, the ortho-nitro derivative showed Emin values of -7.5 kcal/mol for the E. coli PDF complex and -7.9 kcal/mol for the S. aureus PDF complex, surpassing the activity of the standard inhibitor actinonin (Emin = -6.7 kcal/mol). Hydroxy-substituted derivatives demonstrated moderate activity, whereas the introduction of a methoxy group into the aryl fragment decreased the affinity of the ligands toward the enzyme.
Conclusions. A clear structure – activity relationship (SAR) was established, indicating that antimicrobial activity increases in the order of aryl substituents: -OCH3 < -OH < -NO2. The ortho-nitro derivative proved to be the most promising, forming multiple hydrogen bonds, π-cation and hydrophobic interactions with amino acid residues in the catalytic site of PDF. The obtained results can be used for the further design and optimization of novel peptide deformylase inhibitors of bacterial origin.
References
Abdelli A, Azzouni S, Plais R, Gaucher A, Efrit ML, Prim D. Recent advances in the chemistry of 1,2,4-triazoles: Synthesis, reactivity and biological activities. Tetrahedron Lett. 2021;86:153518. doi: https://doi.org/10.1016/j.tetlet.2021.153518
Dai J, Tian S, Yang X, Liu Z. Synthesis methods of 1,2,3-/1,2,4-triazoles: A review. Front Chem. 2022;10:891484. doi: https://doi.org/10.3389/fchem.2022.891484
Zarenezhad E, Farjam M, Iraji A. Synthesis and biological activity of pyrimidines-containing hybrids: focusing on pharmacological application. J Mol Struct. 2021;1230:129833. doi: https://doi.org/10.1016/j.molstruc.2020.129833
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.
Slivka MV, Korol NI, Fizer MM. Fused bicyclic 1,2,4-triazoles with one extra sulfur atom: Synthesis, properties, and biological activity. J Heterocyclic Chem. 2020:1-19. doi: https://doi.org/10.1002/jhet.4044
Marinescu M. Benzimidazole-Triazole Hybrids as Antimicrobial and Antiviral Agents: A Systematic Review. Antibiotics (Basel). 2023;12(7):1220. doi: https://doi.org/10.3390/antibiotics12071220
Gotsulya A, Zaika Y, Brytanova T. Synthesis, properties and biological potential some condensed derivatives 1,2,4-triazole. Ank Univ Eczaci Fak Derg. 2022;46(2):308-21. doi: https://doi.org/10.33483/jfpau.971602
Ogloblina MV, Bushueva IV, Martynyshyn VP, Parchenko VV, Soloviov SO, Gladisheva SA. [Development of industrial production technology with determination of the quality of a soft medicine “Vetmikoderm” for veterinary]. Farmatsevtychnyi Zhurnal. 2023;(6):83-93. Ukrainian. doi: https://doi.org/10.32352/0367-3057.6.23.06
Patil S.A., Nesaragi AR., Rodríguez-Berrios RR., Hampton SM., Bugarin A., Patil SA. Coumarin Triazoles as Potential Antimicrobial Agents. Antibiotics. 2023;12(1):160. doi: https://doi.org/10.3390/antibiotics12010160
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: https://doi.org/10.3390/ ph15081026
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: https://doi.org/10.1016/j.bioorg.2020.104271
Mosleh AA, Dakhel ZA. In silico study, Synthesis, Characterization and Preliminary Evaluation of Antimicrobial activity of new sulfonamide – 1,2,4-triazole derivatives. Iraqi J Pharm Sci. 2025;33(4SI):321-35. doi: https://doi.org/10.31351/vol33iss(4SI)pp321-335
Uygun Cebeci Y. Design, synthesis, and biological evaluation of 1,2,4-triazole derivatives as potential antimicrobial agents. Kocaeli Journal of Science and Engineering. 2023;6(1):69-77. doi: https://doi.org/10.34088/kojose.1060112
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. Ank Univ Eczaci Fak Derg. 2020;44(2):211-9. doi: https://doi.org/10.33483/jfpau.616116
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: https://doi.org/10.14739/2409-2932.2021.3.243176
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.
Biovia. Discovery Studio Visualizer, v 19.1.0.18287 [Software]. 2019. Available from: http://www.3dsbiovia.com
ChemAxon. MarvinSketch, Version 6.3.0. [Software]. 2015. Available from: http://www.chemaxon.com
Worldwide Protein Data Bank. (n.d.). Protein Data Bank (PDB) [Database]. Available from: http://www.pdb.org
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