Pharmaceuticals, cilt.19, sa.2, 2026 (SCI-Expanded, Scopus)
(1) Background: This study evaluates the anticancer potential of a newly synthesized azomethine-based compound, 6,6′,5,8-Dioxa-2,11-diazadodeca-1,11-diene-1,12-diyl)bis(4-bromo-2-methoxyphenol) (B-134-0), against osteosarcoma (SAOS-2) cells, focusing on its effects on apoptosis and DNA-damage-related gene expression. (2) Methods: B-134-0 was synthesized via condensation and tested at eight concentrations (0.5–100 μg/mL) for 24, 48, and 72 h. Cytotoxicity was assessed through MTT assay, and gene expression levels of TP53, RAD51, BRCA2, CASP2, MYC, MDM2, CDKN1A, ERCC1, ATR, and PRKDC were quantified through qPCR using the ΔΔCt method. Molecular docking and DFT analyses were performed to explore structural stability and protein interactions. (3) Results: B-134-0 exhibited strong time-dependent cytotoxicity (IC50: 71.58, 54.36, and 12.59 μg/mL at 24, 48, and 72 h, respectively) and significantly modulated the expression of cell cycle and DNA-repair-associated genes. The compound notably downregulated TP53, RAD51, CASP2, MYC, and MDM2, while CDKN1A and BRCA2 showed relative upregulation, indicating activation of the DNA damage response. Docking results revealed strong binding affinity with BRCA2 and CDKN1A, consistent with experimental findings. (4) Conclusions: These results indicate that B-134-0 exhibits potent anticancer activity by modulating DDR and apoptosis pathways, with strong molecular stability, suggesting its promise as a therapeutic candidate for osteosarcoma.