Advances and Applications in Bioinformatics and Chemistry (Aug 2023)
Synthesis, Biological Evaluation and Molecular Docking Studies of Novel Series of Bis-1,2,4-Triazoles as Thymidine Phosphorylase Inhibitor
Abstract
Nataliya Korol,1 Oksana M Holovko-Kamoshenkova,1 Mikhailo Slivka,1 Oleksandra Pallah,2 Mykhailo Yu Onysko,1 Andriy Kryvovyaz,1 Nadiya V Boyko,2 Olha V Yaremko,3 Ruslan Mariychuk4 1Organic Chemistry Department, Educational and Research Institute of Chemistry and Ecology, Uzhhorod National University, Uzhhorod, Ukraine; 2Department of Clinical and Laboratory Diagnostics and Pharmacology, Faculty of Dentistry, Uzhhorod National University, Uzhhorod, Ukraine; 3Department of Microbiology and Virology, Lviv National Stepan Gzhytsky University of Veterinary Medicine and Biotechnology, Lviv, Ukraine; 4Department of Ecology, Faculty of Humanities and Natural Science, University of Presov, Presov, Slovak RepublicCorrespondence: Nataliya Korol, Organic Chemistry Department, Educational and Research Institute of Chemistry and Ecology, Uzhhorod National University, Tomchaniia Street, 13, Uzhhorod, 88001, Ukraine, Tel +380 95 704 34 56, Email [email protected]: Heterocyclic compounds have diverse biological activities and potential in drug development. This study aims to synthesize novel compounds with two 1,2,4-triazole cores and evaluate their biological properties, particularly their inhibitory activity against thymidine phosphorylase (TP), an enzyme involved in various physiological processes.Methods: The compounds were synthesized by reacting 5,5’-butane-bis-1,2,4-triazole derivatives with prenyl bromide. Characterization involved various techniques, including spectroscopy and elemental analysis. Antimicrobial potential was evaluated against bacteria and fungi, with comparative antibiotics as references. Inhibitory activity against TP was assessed, and molecular docking studies were conducted.Results: Six compounds were successfully synthesized and their structures confirmed. The synthesized triazole derivatives exhibited high biological activity, with compounds 2 and 6 showing the most promising TP inhibition. Molecular docking studies revealed interactions between compound 2 and TP, involving nine amino acids.Discussion: The synthesis of novel compounds with two 1,2,4-triazole cores contributes significantly to bis-triazole research. These compounds have potential as anti-tumor agents due to their inhibitory activity against TP, a crucial enzyme in tumor growth and metastasis. Comparative evaluation against antibiotics highlights their potency. Docking results provide insights into their interactions with TP, supporting their potential as potent TP inhibitors. Further research should focus on evaluating their efficacy in biological models, understanding their mechanisms of action, and optimizing their activities.Conclusion: The synthesized compounds with two 1,2,4-triazole cores exhibit significant biological activity, including strong TP inhibition and broad-spectrum antimicrobial effects. These findings emphasize their potential as anti-tumor agents and the need for further exploration and optimization. Future research should focus on evaluating their efficacy in biological models, understanding their mechanisms of action, and developing more potent bis-triazole derivatives for drug discovery efforts. The combined results from assays and docking studies support the therapeutic potential of these compounds as anti-tumor agents.Keywords: alkylations, antitumor agents, heterocycles, hydrogen bonds, molecular modelling
