Comparative Biological Activity of a Set of Copper(II), Nickel(II) and Cobalt(II) Complexes with Thiazole Based Ligands

Limitations of current cancer treatments arise from severe toxicity, lack of selectivity, and drug resistance. Metal-based drugs are an important class of cancer therapeutics since the metal ion can interact with biological molecules in ways that traditional organic drugs cannot. As such, the development of new metal-based anticancer agents with improved selectivity and alternative mechanisms of action is highly desirable. Beyond cisplatin, which utilizes a platinum(II) metal center, first-row transition metal ions such as copper(II), nickel(II), cobalt(II), and zinc(II) offer diverse coordination chemistry, tunable redox properties, and biological relevance, making them promising candidates for next-generation metallodrugs. The current structure-function studies aim to investigate how both the metal center and ligand backbone influence coordination chemistry and biological activity. The synthesis of a series of Cu(II), Ni(II), Co(II) and Zn(II) complexes with thiazole containing ligands were attempted. The products of Cu(II), Ni(II), and Co(II) complexes were characterized using infrared and UV/Vis spectroscopies, elemental analysis, and single-crystal X-ray diffraction, while no Zn(II) complexes could be isolated. Comparative studies within this set enables systematic evaluation of biological activity based on electronic structure, coordination geometry, and ligand design. Thus far, the cytotoxic evaluation of the free ligands and the corresponding Cu(II) and Co(II) complexes has been carried out using MTT cell viability assays in HeLa cells, a commonly used test that measures how effectively compounds reduce cancer cell survival. Preliminary results indicate that metal coordination of the thiazole ligands enhance cytotoxic activity and variations in the ligand backbone alter cytotoxic effects of the metal complexes. The results of these studies will be presented along with a comparative analysis of previously reported complexes. Future work will include cytotoxicity screening in additional cancer cell lines and reactive oxygen species detection assays to examine potential redox-related mechanisms. Additionally, DNA-binding and cleavage studies will be performed to further elucidate structure-activity relationships and mechanisms of action within the set to guide rational metallodrug design for the next generation of metallo-chemotherapeutics.