Search for molecular descriptors and computer prediction of biological activity in a series of S-derivatives (1,2,4-triazole-3(2H)-yl)methyl)thiopyrimidines

Authors

DOI:

https://doi.org/10.14739/2409-2932.2024.1.298027

Keywords:

1,2,4-triazole, pyrimidine, S-derivatives, biological activity, antihypertensive agents

Abstract

Most pharmaceutical compounds interact with various molecular compositions in the body, leading to complex biological effects. Furthermore, during biotransformation, they may generate one or more metabolites with potent bioactive properties. Therefore, the development and careful use of new medications require thorough examination of their biological impact profiles, including considerations of human metabolic processes. In silico techniques are currently widely used to evaluate the interactions of emerging drug candidates with pharmacological conditions and predict their metabolic conversions. To investigate the bioactivity of compounds based on the structure of 1,2,4-triazole-3(2H)-thione with pyrimidine-2-thiol, we generated a combinatorial library of bioregulators using the computer programs SuperPred and SwissADME. The relevance of this research is underscored by the ongoing quest for novel biomolecular compounds that are highly effective yet low in toxicity, spanning both natural and synthetic sources. Much attention is directed towards nitrogen-containing heterocycles, particularly derivatives of 1,2,4-triazole, due to their substantial medical and biological potential.

The aim of the work is to create a combinatorial library of bioregulators, which contains the structures of 1,2,4-triazole and pyrimidine, and to carry out in silico screening of heterocycle derivatives using the SuperPred web server to determine promising directions for the study of their bioactivity.

Materials and methods. The subject of our research is S-derivatives of (1,2,4-triazole-3(2H)-yl)methyl)thiopyrimidines. Virtual screening of compounds was carried out using the SuperPred computer program. The ADME study was performed using the free service SwissADME, which is used to evaluate the pharmacokinetics, bioavailability, and interaction of small molecules with enzymes in medicinal chemistry.

Results. Predicting the likelihood of a substance demonstrating a particular biological activity enables the selection of the most appropriate tests for studying the activity of a given chemical compound, as well as identifying which substances available to the researcher are most likely to enhance the effectiveness of the effects. This principle is grounded in the concept that “the biological activity of a substance is a function of its chemical structure”. Such predictions are generated based on the structural formula of a chemical compound and can be made during the planning stage of synthesis.

Conclusions. A combinatorial library of bioregulators was created by combining the structure of 1,2,4-triazole-3(2H)-thione with pyrimidine-2-thiol. The conducted virtual screening of the 1,2,4-triazole-3(2H)-thione heterocycle with pyrimidine-2-thiol shows promise for obtaining non-toxic compounds with antineoplastic biological activity. Screening of derivatives, particularly S-derivatives of (1,2,4-triazole-3(2H)-yl)methyl)thiopyrimidines, indicates the potential for discovering biologically active substances with antineoplastic, antibacterial, analgesic, antidiabetic, antihypertensive, and other types of biological activities within this compound series.

Author Biographies

Yu. V. Karpenko, Zaporizhzhia State Medical and Pharmaceutical University, Ukraine

PhD, Senior Lecturer of the Department of Natural Sciences for Foreign Students and Toxicological Chemistry

O. I. Panasenko, Zaporizhzhia State Medical and Pharmaceutical University, Ukraine

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

A. P. Litun, Zaporizhzhia State Medical and Pharmaceutical University, Ukraine

student of the 6th year

References

Panasenko OI, Odyntsova VM, Hotsulia AS. [In silico evaluation of the pharmacodynamic component of the interaction of S-alkyl derivatives of 5-methyl-4-(p-tolyl)-1,2,4-triazole-3-thiol with some biological targets]. Current issues in pharmacy and medicine: science and practice. 2023; 16(3):223-30. Ukrainian. doi: https://doi.org/10.14739/2409-2932.2023.3.287510

Varynskyi B, Parchenko V, Kaplaushenko A, Panasenko O, Knysh Y. Development and validation of a LC-ESI-MS method for detection of piperidin-1-ium {[5-(2-furyl)-4-phenyl-4H-1,2,4-triazol-3-yl]thio}acetate residues in poultry eggs. Ankara Universitesi Eczacilik Fakultesi Dergisi. 2016;40(3):29-40. doi: https://doi.org/10.1501/Eczfak_0000000586

Karpenko YV, Panasenko OI. Search for antibacterial activity in a number of new S-derivatives (1,2,4-triazole-3(2H)-yl)methyl) thiopyrimidines. Current issues in pharmacy and medicine: science and practice. 2021;14(2):173-8. doi: https://doi.org/10.14739/2409-2932.2021.2.234565

Zazharskyi V, Parchenko M, Parchenko V, Davydenko P, Kulishenko O, Zazharska N. Physicochemical properties of new S-derivatives of 5-(5-bromofuran-2-yl)-4-methyl-1,2,4-triazol-3-thiols. Voprosy khimii i khimicheskoi tekhnologii. 2020;6:50-8. doi: https://doi.org/10.32434/0321-4095-2020-133-6-50-58

Karpenko YV, Panasenko OI, Kulish SM, Domnich AV. Synthesis and acute toxicity of new S-derivatives (1,2,4-triazole-3(2H)-yl)methyl) thiopyrimidines. Current issues in pharmacy and medicine: science and practice. 2023;16(2):158-64. doi: https://doi.org/10.14739/2409-2932.2023.2.274586

Nickel J, Gohlke BO, Erehman J, Banerjee P, Rong WW, Goede A, et al. SuperPred: update on drug classification and target prediction. Nucleic Acids Res. 2014;42(Web Server issue):W26-31. doi: https://doi.org/10.1093/nar/gku477

Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2017;7:42717. doi: https://doi.org/10.1038/srep42717

Khilkovets A, Karpenko Y, Bigdan O, Parchenko M, Parchenko V. Synthetic and biological aspects of studying the properties of 1,2,4-triazole derivatives. Scientific Journal of Polonia University. 2022;51(2):324-31. doi: https://doi.org/10.23856/5138

Published

2024-02-23

How to Cite

1.
Karpenko YV, Panasenko OI, Litun AP. Search for molecular descriptors and computer prediction of biological activity in a series of S-derivatives (1,2,4-triazole-3(2H)-yl)methyl)thiopyrimidines. Current issues in pharmacy and medicine: science and practice [Internet]. 2024Feb.23 [cited 2024Jun.21];17(1):5-9. Available from: http://pharmed.zsmu.edu.ua/article/view/298027