Combinatorial Synthesis toward the Discovery of Highly Cytotoxic Fe(III) Complexes

Cancer remains one of the deadliest diseases worldwide, with some tumors proving difficult to treat and increasingly resistant to current therapies. Capitalizing on this, there is a need for new therapeutic agents with novel mechanisms of action. Among promising candidates, Fe(III) complexes have gained significant attention as potential chemotherapeutic agents. However, research on these compounds has been limited to a small number, leading to inefficiencies in drug discovery. This study addresses these limitations by developing a combinatorial library of 495 new Fe(III) complexes synthesized from aminophenol, hydroxybenzaldehyde, and pyridine derivatives. The compounds were screened for cytotoxicity against human breast adenocarcinoma and noncancerous fibroblasts, identifying a novel class of Fe(III) complexes with modest cancer cell selectivity. The lead compound effectively eradicated breast cancer tumor spheroids at low micromolar concentrations, highlighting the potential of this approach for rapid drug discovery.