Biological studies of heterobimetallic complexes as hypoxia-activated anticancer prodrugs

Abstract

Cancer remains a major cause of death worldwide, and while Pt(II) drugs like cisplatin are effective, their lack of selectivity leads to significant side effects. To address this, researchers are exploring alternative metal complexes with better targeting, such as Co(III) compounds that act as hypoxia-activated prodrugs. These complexes remain inactive in normal oxygen conditions but become activated in the low-oxygen environment of tumors, releasing a cytotoxic ligand derived from the iron chelator Deferiprone. In this study, newly synthesized Co(III)-based complexes and the ligand were tested on MCF-7 breast cancer cells under both normoxic and hypoxic conditions using cytotoxicity assays and RT-qPCR. Results showed that the Co(III) complex exhibited selective activation under hypoxia, with reduced toxicity in normal conditions, while the ligand induced gene expression consistent with iron chelation. Overall, the findings suggest that Co(III) complexes could serve as targeted carriers for anticancer agents, and iron chelators may also have therapeutic potential.