Authors: N. M. Borysenko | І. V. Bushueva | В. В. Парченко | О. P. Shmatenko | А. М. Solomennyi | О. К. Yerenko | O. P. Kileyeva
Source: Ukrainian Journal of Military Medicine (article, 2025-06-30)
Field: Chemistry — Organic Chemistry

In silico study of biological activity of 2-[5-(furan-2-yl)-4-phenyl-4n-1,2,4-triazol-3-ylthio]-1-(4-chlorophenylethanone) Introduction. In modern conditions, where military conflicts are accompanied by significant psychological and physical stress on participants, the development of effective antiepileptic drugs has become one of the key challenges in medicine. This issue is particularly relevant due to the increasing number of cases of traumatic brain injuries, concussions, and other stress-related damages that can provoke convulsive states. In this context, derivatives of 1,2,4-triazole, which possess a broad spectrum of biological activity, including anticonvulsant effects, appear promising for the creation of new pharmaceutical agents capable of meeting the needs of military medicine. The purpose of the study was to investigate the biological activity of 2-[5-(furan-2-yl)-4-phenyl-4H-1,2,4-triazol-3-ylthio]-1-(4-chlorophenyl)ethanone using computer-based predictive methods. This approach allows to determine the presence of new types of activity, which could expand scientific research pathways and establish a promising direction for further testing of this molecule. Materials and methods. Molecular docking was performed using Autodock 4.2.6. For screening, the crystallographic structures of GABAA receptors –“4COF,” “6D6T,” and “6X3U” - obtained from the RCSB Protein Data Bank were used. Visualization of the results was conducted using Schrödinger Release 2018-1: Schrödinger, LLC, New York, NY, 2018. The grid parameters for binding were 30 Å × 30 Å × 30 Å, and the grid center coordinates were: 4COF (7 Å × 12 Å × 132 Å), 6D6T (119 Å × 181 Å × 126 Å), 6X3U (137 Å × 108 Å × 142 Å), which provided a sufficiently large space to encompass the receptor center. The ADME evaluation was performed using the free SwissADME tool, which is widely used in medicinal chemistry for analyzing pharmacokinetics, bioavailability, and interactions of small molecules with enzymes. This service considers six physicochemical characteristics: lipophilicity, size, polarity, solubility, flexibility and saturation. Each of these characteristics has its own physicochemical range, which is visualized as a pink zone on the radar plot. For a molecule to be considered drug-like, its radar profile must be entirely within this zone. Results. The study of the interaction of the selected compound with GABAA receptors (4COF, 6D6T, 6X3U) demonstrated its ability to stably bind to the active sites of the receptors, as evidenced by binding energies ranging from –6.119 to –8.559 kcal/mol. The main interactions include hydrophobic contacts, hydrogen bonds, and electrostatic interactions, indicating the compound's potential to modulate receptor activity. The high binding energy values, particularly for the 6X3U structure, suggest the possibility of effectively influencing neuronal excitability, which is promising for the development of antiepileptic agents. The obtained results confirm that the selected compound has potential for further research as a candidate for the development of new pharmaceutical drugs. Conclusions. The pharmacokinetic analysis demonstrated favourable bioavailability characteristics of the compound, including optimal lipophilicity, solubility, and molecular size, in accordance with the parameters typical for pharmaceutical drugs. This enhances the prospects for further investigation of the compound in experimental epilepsy models and for the development of new anticonvulsant drugs based on it. The use of computer modelling significantly accelerates the selection of promising compounds, reduces drug development costs, and contributes to the creation of more effective medications for military personnel in the future. Furan ; In silico ; Chemistry ; Triazole ; Stereochemistry ; Combinatorial chemistry ; Organic chemistry ; Biochemistry ; Gene Synthesis and biological activity ; Synthesis and Characterization of Heterocyclic Compounds ; Computational Drug Discovery Methods