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

Abstract

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.

Keywords

• 1 2 4-triazole
• design
• adme analysis
• molecular modeling