Study of ADME characteristics of thioderivatives of 3,5-bis(5-mercapto-4-R-4H-1,2,4-triazol-3-yl)phenol
DOI:
https://doi.org/10.14739/2409-2932.2025.3.339936Keywords:
1,2,4-triazole derivatives, ADME, drug-likeness, CYP inhibition, antioxidant potential, antihypoxic activityAbstract
This study investigates the ADME properties of newly synthesized derivatives of 3,5-bis(5-mercapto-4-R-4H-1,2,4-triazol-3-yl)phenols and their alkylated analogues.
Aim: to evaluate the effect of structural modifications, such as alkylation, chain elongation, and introduction of substituents, on absorption, distribution, metabolism, and excretion parameters, with an emphasis on drug-likeness and medicinal potential.
Materials and methods. Computational approaches using SwissADME tools were applied to predict key physicochemical and pharmacokinetic descriptors, including molecular weight, TPSA, lipophilicity (LogP), solubility, gastrointestinal absorption, P-glycoprotein substrate recognition, and cytochrome P450 (CYP) inhibition profiles. Radar plots and comparative tables were employed to visualize differences between structural analogues.
Results. The analysis showed that most derivatives maintain acceptable lipophilicity and solubility ranges, while some analogues demonstrated promising profiles in terms of balanced polarity and molecular size. Several compounds were predicted as potential inhibitors of CYP3A4 and CYP2C9 isoenzymes, highlighting their possible pharmacological activity. Despite moderate limitations in oral bioavailability, certain molecules exhibited favorable characteristics suggesting a good balance between stability and pharmacokinetic behavior. Structural features, such as alkyl chain length and substitution patterns, significantly influenced solubility, permeability, and drug-likeness scores. The data suggest that further optimization of polarity and molecular weight could improve gastrointestinal absorption while retaining beneficial pharmacological interactions. The antioxidant and antihypoxic potential of these molecules is supported by their structural features and predicted bioactivity, positioning them as attractive candidates for future biological screening.
Conclusions. The study provides a computational basis for selecting the most promising triazole-based derivatives for subsequent in vitro and in vivo testing, facilitating the design of compounds with optimized ADME properties and potential therapeutic application.
References
Gridan IM, Ciorsac AA, Isvoran A. Prediction of ADME-Tox properties and toxicological endpoints of triazole fungicides used for cereals protection. ADMET DMPK. 2019;7(3):161-73. doi: https://doi.org/10.5599/admet.668
Şahin İ, Çeşme M, Yüce N, Tümer F. Discovery of new 1,4-disubstituted 1,2,3-triazoles: in silico ADME profiling, molecular docking and biological evaluation studies. J Biomol Struct Dyn. 2023;41(5):1988-2001. doi: https://doi.org/10.1080/07391102.2022.2025905
Çakmak Ü, Öz Tuncay F. Antityrosinase activities and in silico ADME properties of fluorine-containing 1,2,4-triazole-5-on derivatives. Hacet J Biol Chem. 2022;50(4):319-24. doi: https://doi.org/10.15671/hjbc.1053348
Martynyshyn VP, Hunchak VM, Gutyj BV, Rudenko OP. [Prediction of biological activity of 4-(3,4-dimethoxybenzylidene)amino-5-(2-fluorophenyl)-4H-1,2,4-triazole-3-thiol]. Scientific Messenger of LNU of Veterinary Medicine and Biotechnologies. Series: Veterinary Sciences. 2024;26(116):255-9. Ukrainian. doi: https://doi.org/10.32718/nvlvet11637
Gotsulya A. Synthesis and antiradical activity of alkyl derivatives of 5-(5-methyl-1H-pyrazol-3-yl)-4-phenyl-4h1,2,4-triazole-3-thiol. Ank Univ Eczaci Fak Derg. 2020;44(2):211-9. doi: https://doi.org/10.33483/jfpau.616116
Sameliuk Y, Isaycheva K, Kaplaushenko A. Synthesis, determination of physico-chemical parameters, structure confirmation, and antioxidant activity of compounds based on 3,5-bis(5-mercapto-4-R-4H-1,2,4-triazole-3-yl)phenol. ScienceRise: Pharmaceutical Science. 2024;5:63-70. doi: https://doi.org/10.15587/2519-4852.2024.313832
Isaycheva KK, Kaplaushenko AG, Sameliuk YG, Shmatenko OP, Solomennyi AM. Antioxidant agents in wartime: prospects for the development of new biologically active compounds based on 1,2,4-triazole derivatives. Ukrainian Journal of Military Medicine. 2025;6(2):125-33. doi: https://doi.org/10.46847/ujmm.2025.2(6)-125
Kalchenko VV, Shcherbyna RО, Panasenko OI, Salionov VО, Morozova LP. Evaluation of the antioxidant potential of some 5-(2-bromo-4-fluorophenyl)-4-ethyl-1,2,4-triazole-3-thiol derivatives. The Odessa Medical Journal. 2024;(5):89-94. https://doi.org/10.32782/2226-2008-2024-5-15
Safonov A, Demianenko D, Vashchyk Y, Lytkin D, Polonets O, Kosareva A, et al. Study of the stress-protective effect of sodium 2-((4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazol-3-yl)thio)acetate. Hacet Univ J Fac Pharm. 2024;44(2):143-52. doi: https://doi.org/10.52794/hujpharm.1374871
Gotsulya A, Zaika Y, Brytanova T. Synthesis, properties and biological potential some condensed derivatives 1,2,4-triazole. Journal of Faculty of Pharmacy of Ankara University. 2022;46(2):308-21. doi: https://doi.org/10.33483/jfpau.971602
Downloads
Additional Files
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 K. K. Isaicheva, A. H. Kaplaushenko
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
