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.