Akademik Veri Yönetim Sistemi
Journal of Molecular Structure, cilt.1361, 2026 (SCI-Expanded)
Breast cancer remains a major health challenge due to the heterogeneity of tumor subtypes and the limited efficacy of single-target therapeutic approaches. In this study, a new series of polymethoxy rhodanines was designed and synthesized, and their anticancer potential was evaluated against MCF-7 and MDA-MB-231 breast cancer cell lines, together with healthy HEK-293 cell line. Among the tested derivatives, compound 2 emerged as the most promising candidate, exhibiting potent cytotoxic activity against MCF-7 (IC50 = 17.38 ± 2.02 µM) and MDA-MB-231 (IC50 = 27.30 ± 1.04 µM) cells, along with high selectivity indices of 30.8 and 19.6, respectively, compared to HEK-293 cells. To predict the molecular basis of its activity, compound 2 was subjected to computational studies targeting estrogen receptor alpha (ERα) and vascular endothelial growth factor receptor 2 (VEGFR2). Induced-fit docking and MMGBSA calculations revealed favorable binding free energies for compound 2 against ERα (ΔGbind = -85.18 kcal/mol) and VEGFR2 (ΔGbind = 85.64 kcal/mol), outperforming the reference drug sorafenib. Molecular dynamics simulations further confirmed the stability of both complexes, with low RMSD values (2.0 Å for ERα and 1.4 Å for VEGFR2) and persistent key interactions throughout the simulation. In silico ADME predictions demonstrated that compound 2 possesses favorable pharmacokinetic properties, including high predicted oral absorption (100%) and acceptable drug-likeness parameters, comparable to sorafenib. This study provides experimental and computational evaluation of a promising anticancer scaffold and offers mechanistic insight into its interaction with molecular targets relevant to distinct breast cancer subtypes, highlighting compound 2 as a potential lead for further optimization.