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

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(Me₂bpy)₂(N₃)₂]⁺, featuring 5,5'-dimethyl-2,2'-bipyridyl (Me₂bpy) 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; IC₅₀ = 29.9 µM) and human cervical cancer cells (ME-180; IC₅₀ = 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.