Chemistry and Biodiversity, cilt.22, sa.9, 2025 (SCI-Expanded, Scopus)
Cancer stem cells (CSCs) drive tumor initiation, metastasis, drug resistance, and recurrence, making them critical therapeutic targets. This study investigated two isoeugenol-derived polyphenolic compounds, designated as 1 and 2, in breast, prostate, and colon CSCs using monolayer and three-dimensional tumoroid models. After 48 h, both compounds significantly inhibited proliferation. In prostate cancer cells, compound 2 exhibited a lower half-maximal inhibitory concentration (17.18 µM) than compound 1 (21.04 µM) and 5-fluorouracil (5-Fu) (21.51 µM). In three-dimensional tumoroids, compound 2 reduced tumoroid diameters by an additional 8% compared to 5-Fu. Molecular docking with AutoDock 4.2 revealed strong interactions between both compounds and key stemness regulators Sox2, Oct4, and Nanog. Compound 2 displayed the most favorable binding energies (−6.31 kcal/mol for Oct4, −5.36 for Nanog, and −4.62 for Sox2), suggesting stable complex formation that may disrupt core transcription factors. These findings support further investigation of polyphenol derivatives as potential CSC-targeting agents, with additional in vivo and pharmacokinetic studies needed to confirm therapeutic viability.