Title New hybrid pyridine-1,2,4-triazole scaffolds: synthesis, in vitro evaluation of anticancer and antimicrobial activity, and in silico insights
Authors Šermukšnytė, Aida ; Lukauskas, Dainius ; Stasevych, Maryna ; Zvarych, Viktor ; Komarovska-Porokhnyavets, Olena ; Kantminienė, Kristina ; Tumosienė, Ingrida ; Petrikaitė, Vilma
DOI 10.1038/s41598-026-53201-3
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Is Part of Scientific reports.. Berlin : Nature portfolio. 2026, Early access, p. 1-31.. eISSN 2045-2322
Keywords [eng] Acetamide ; Antimicrobial activity ; Cell migration ; Cell viability ; Selectivity ; Tumour spheroids
Abstract [eng] 1,2,4-Triazole-3-thiones bearing 2-amino-5-chloropyridine or 2-amino-3,5-dibromopyridine moieties were S-alkylated with substituted bromoacetamides to obtain target 1,2,4-triazole-3-thiols. Anticancer effects of the synthesized compounds were evaluated in vitro using cell monolayer (MTT and 'wound healing' assays) and 3D spheroid models against human lung adenocarcinoma (A549), triple-negative breast cancer (MDA-MB-231), and melanoma (IGR39) cell lines. In the initial screening, compounds incorporating the 3,5-dibromopyridyl fragment were generally the most cytotoxic and compound 34 (5-chloropyridinyl derivative) was the most potent, with EC50 values below 5 µM for all tested cancer cell lines. Although cytotoxic, they did not markedly inhibit cancer cell migration. In 3D spheroid cultures, 34 significantly inhibited the growth of MDA-MB-231 and IGR39 spheroids, while compounds 24 (phenyl) and 26 (p-tolyl) decreased spheroid viability without altering their size. Compound 26 also demonstrated notable antimicrobial properties, exhibiting stronger antifungal activity against C. tenuis (7.8 µg/mL) than nystatin (15.6 µg/mL) and matching the antibacterial potency of vancomycin against M. luteum (7.8 µg/mL). Molecular docking suggested possible MEK/BRAF-related interactions within the mitogen-activated protein kinase pathway. Compound 34 showed the most favourable predicted binding profile for MEK (-11.134 kcal/mol) and BRAF (-10.336 kcal/mol). However, these in silico findings require to be confirmed experimentally.
Published Berlin : Nature portfolio
Type Journal article
Language English
Publication date 2026
CC license CC license description