Iron-cyclopentadienyl compounds with nitrile-based ligands show strong activity against a broad panel of human cancer cell lines

Cancer is one of the deadliest diseases worldwide. Currently, platinum-based drugs are the most used chemotherapeutics, alone or in conjugation with other drugs. However, many noxious side effects are associated to their use. In that frame, the use of biologically essential metals, such as iron, seems a valuable strategy.

A cationic family of piano stool iron-cyclopentadienyl complexes with the general formula [Fe(η⁵-Cp)(CO)(PR₃)(NCR)]⁺, where NCR = 4-aminobenzonitrile and PR₃ = triphenylphosphane, 4-(diphenylphosphino)benzoic acid or tris(4-fluorophenyl) phosphane, has been developed with the main purpose of studying the effect that the different substituents on the phosphane ligand had on the compounds’ anticancer activity. Given the promising preliminary results in terms of activity obtained for the compound bearing triphenylphosphane in human cervical cancer line HeLa, further compounds were synthesized by changing the nature of nitrile allowing the synthesis of six new compounds with the general formula [Fe(η⁵-Cp)(CO)(PPh₃)(NCR)]⁺ (NCR = nitriles with different substituents). The compounds biological activity was tested in two different tumor cell lines, namely breast MDA-MB-231 and colorectal SW480, and in the normal colon-derived cell line NCM460. All compounds were cytotoxic in the micromolar range, showing an intrinsic selectivity for the SW480 line (vs. NCM460). Further studies in the SW480 cell line have shown that the compounds induce cell death by apoptosis and inhibit proliferation by hindering the formation of colonies and affecting the cytoskeleton of cells.