| E1 / Čes. slov. Farm. 2025;74(3):E1-E5 / ČESKÁ A SLOVENSKÁ FARMACIE www.csfarmacie.cz PŮVODNÍ PRÁCE ADME Profile Calculation and Drug Similarity Study of New 1,2,4-Triazole Derivatives Containing 2-Bromo-5-Methoxyphenyl Radical https://doi https:// .org/10.36290/csf.2025.024 ADME Profile Calculation and Drug Similarity Study of New 1,2,4-Triazole Derivatives Containing 2-Bromo-5-Methoxyphenyl Radical Mykola Skoryi1, Roman Shcherbyna1, Sergii Kulish1, Volodymyr Salionov2, Oleksandra Cherchesova3 1Department of Toxicological and Inorganic Chemistry, Faculty of Pharmacy, Zaporizhzhia Medical and Pharmaceutical University, Zaporizhzhya, Ukraine 2Department of Biological Chemistry, Faculty of Pharmacy, Zaporizhzhia Medical and Pharmaceutical University, Zaporizhzhya, Ukraine 3Professional Medical and Pharmaceutical College of PJSC „Higher Education Institution“ MAUP, Kyiv, Ukraine Introduction: Evaluating ADME (absorption, distribution, metabolism, excretion) profiles is critical in drug development to ensure bioavailability, efficacy, and safety. 1,2,4-Triazole derivatives, particularly those with a 2-bromo-5-methoxyphenyl radical, are promising due to their broad biological activities, yet their pharmacokinetic properties are insufficiently studied. The objective of this study was to predict the ADME characteristics and drug-likeness of these compounds to identify candidates with optimal pharmacokinetic potential for therapeutic applications. Objectives: This study aimed to assess the ADME profiles of new 1,2,4-triazole derivatives incorporating a 2-bromo-5-methoxyphenyl fragment using in silico methods and evaluate their compliance with drug-likeness criteria, such as Lipinski’s Rule of 5, for potential pharmaceutical development. Methods: A series of 28 derivatives, including 5-(2-bromo-5-methoxyphenyl)-4-R-1,2,4-triazole-3-thiols (3a–3d), thioacetic acids (4a–4d), and esters (5a–5t), were analyzed via the Molinspiration Property Calculator. Key parameters assessed were lipophilicity (miLogP), polar surface area (TPSA), molecular weight (MW), hydrogen bond donors (nOHNH) and acceptors (nON), rotatable bonds (nrotb), and Lipinski rule violations (nviolations). Results: Thiol derivatives (3a–3d) showed moderate lipophilicity (miLogP 3.02-3.33) and TPSA (39.95–50.81 Ų), suggesting good permeability. Thioacetic acids (4a–4d) had higher TPSA (77.25–88.11 Ų) and lower miLogP (2.46–3.81), indicating enhanced solubility but reduced permeability. Esters (5a–5t) varied widely in lipophilicity (miLogP 3.08–5.86), with three compounds (5l, 5p, 5t) exceeding Lipinski’s miLogP limit (> 5). Most compounds complied with Lipinski’s Rule, with MW ranging from 286.15–476.40 g/mol and nrotb from 2–10. Conclusion: Structural modifications significantly influenced ADME profiles, with thiols and thioacetic acids showing favorable drug-like properties. High-lipophilicity esters may require optimization. These findings support the potential of these triazole derivatives as drug candidates, warranting further pharmacological studies. Key words: 1,2,4-triazole, ADME, in silico, drug-likeness, pharmacokinetics, 2-bromo-5-methoxyphenyl. Výpočet ADME profilu a studie podobnosti s léčivy u nových derivátů 1,2,4-triazolu obsahujících radikál 2-brom-5-methoxyfenyl Úvod: Hodnocení ADME (absorpcí, distribuce, metabolismu a exkrece) je zásadní součástí vývoje léčiv, protože zajišťuje biologickou dostupnost, účinnost a bezpečnost. Deriváty 1,2,4-triazolu, zejména ty obsahující radikál 2-brom-5-methoxyfenyl, jsou perspektivní díky své široké biologické aktivitě, avšak jejich farmakokinetické vlastnosti jsou dosud nedostatečně prozkoumány. Cílem této studie bylo predikovat ADME charakteristiky a podobnost s léčivy u těchto sloučenin, a identifikovat tak kandidáty s optimálním farmakokinetickým potenciálem pro terapeutické využití. Roman Shcherbyna Department of Toxicological and Inorganic Chemistry, Faculty of Pharmacy, Zaporizhzhia Medical and Pharmaceutical University, Zaporizhzhya, Ukraine rscherbyna@gmail.com Cit. zkr: Čes. slov. Farm. 2025;74(3):E1-E5 Článek přijat redakcí: ??? Článek přijat po recenzích: ??? PLNÁ VERZE ČLÁNKU➜ https://doi.org/10.36290/csf.2025.024 POUZE PRO PŘEDPLATITELE ČASOPISU ČESKÁ A SLOVENSKÁ FARMACIE
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