Targeting Cancer Cells With Co(III)‐Bipyridyl Complex: A Combined In Vitro and In Silico Study on U87MG and ME‐180 Cell Lines

ABSTRACT Although some Co‐bipyridyl systems have been explored in anticancer research, further enhancement in the therapeutic index of mixed‐ligand polypyridyl Co III ‐centered compounds is a prime necessity. In this work, a new octahedral cobalt(III) complex, [Co III (Me 2 bpy) 2 (N 3 ) 2 ] + , featuring 5,5'‐dimethyl‐2,2'‐bipyridyl (Me 2 bpy) and coordinated terminal azide ligands, was synthesized and characterized using single crystal x‐ray diffraction and spectroscopic techniques. Density functional theory (DFT) calculations provided insights into the metal–ligand bonding and electronic transitions. Biophysical studies, complemented by molecular docking with calf thymus DNA (ct‐DNA) and human serum albumin (HSA) suggested a strong interaction between the Co III complex and ct‐DNA. In silico toxicological studies demonstrate a safer toxicity profile of Co III complex than paclitaxel, a clinically approved anticancer drug and comparable to Doxovir, a gold‐standard in biologically active Co III ‐species. In vitro MTT assay showed that the Co III complex is more cytotoxic to glioblastoma multiforme (U87MG; IC 50 = 29.9 µM) and human cervical cancer cells (ME‐180; IC 50 = 11 µM) than its controls in a dose‐dependent and apoptotic pathway, with cervical carcinoma cells appearing more susceptible to Co III ‐mediated effects. The results demonstrate that Co III complex significantly enhances the therapeutic potential of paclitaxel through synergistic cytotoxic and antimigratory effects, underscoring its promise as a chemo adjuvant candidate for combinatorial cancer therapy.