246: Comparative biological activity of a set of Copper(II), Nickel(II) and Cobalt(II) complexes with thiazole-based ligands

Abstract: Limitations around current cancer treatments arise from both the severe toxicity, non-specificity, and drug resistance. 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 Pt(II), first-row transition metals 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 the 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 a thiazole containing ligand were attempted. The products of Cu(II), Ni(II), and Co(II) complexes were characterised 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 the set enables systematic evaluation of the biological activity based on the electronic structure, coordination geometry, and ligand structure. 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. Preliminary results indicate that metal coordination of the thiazole enhances cytotoxic activity and differences 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 additional cytotoxicity screening in other cancer cell lines and reactive oxygen species detection assays to correlate redox behavior with observed antiproliferative activity. 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.