Targeting Breast Cancer with Schiff Base Metal Complexes: Synthesis, Structural Characterization, and In-Vitro/In-Silico Validation

A novel bidentate Schiff base ligand (HL), derived from dopamine and 1,4-benzodioxane-6-carboxaldehyde, was employed for the microwave-assisted synthesis of a new series of transition metal complexes: Cu(HL)₂, Co(HL)₂, Ni(HL)₂, and Zn(HL)₂. The rapid, solvent-efficient synthesis yielded high-purity products, which were comprehensively characterized by spectroscopic, diffraction, and thermal analyses. Spectroscopic data confirmed the bidentate coordination of HL via the phenolic oxygen atoms. Among the complexes, Co(HL)₂ exhibited a crystalline structure, while the others were semi-amorphous, all showing stability up to 500°C. In-vitro anticancer screening against breast (MDA-MB-231, MDA-MB-468) and cervical (HeLa) cancer cell lines revealed significant cytotoxicity, with Co(HL)₂ showing the highest potency (IC₅₀: 23.19–25.67 μM) and low toxicity towards normal kidney cells (HEK-293). Computational docking and 100 ns molecular-dynamics simulations demonstrated strong binding affinity and conformational stability of Co(HL)₂ within the ATP-binding site of Janus kinase 2 (JAK2), implicating a possible JAK2-targeted apoptotic pathway. These findings highlight the potential of Co(HL)₂ Schiff base complex as a promising candidate for targeted anticancer therapy.