# The Cytotoxic Activity of Diiron Bis-Cyclopentadienyl Complexes with Bridging C\({}_{3}\)-Ligands
## 3 Conclusions  
The search for new transition metal anticancer drugs, overcoming the limitations associated to the administration of platinum chemotherapies, is an intensively explored field of research, and, in this regard, iron is a convenient choice as a metal element essentially due to its limited intrinsic toxicity. Various iron compounds have been investigated for their anticancer potential, however studies on diiron complexes are still in their infancy, despite several advantages provided by the presence of two cooperating metal centers. Following our recent description of the promising cytotoxic activity of cationic diiron complexes with a bridging vinyliminium ligand, here we report additional studies on a selection of such category of complexes. One compound of the series, containing a phenyl group on the C\({}_{3}\) chain, emerged as an effective cytotoxic agent against a panel of cancer cell lines. Since the mode of action seems ascribable, inter alia, to a slow fragmentation occurring in cells and affording a monoiron vinyl-aminoalkylidene derivative, we monitored the antiproliferative activities of the diiron phenyl precursor and of its monoiron counterpart at different times of incubation. The results support the hypothesis of the fragmentation reaction as one of the possible mechanisms of anticancer action. Then, analyses on neutral diiron complexes containing a selenophene-decorated ligand evidence a scarce influence of the organic moiety on the cytotoxicity, which is presumably best correlated to the redox activity of the iron centers and, eventually, to CO release. In summary, diiron organometallic complexes constitute an arsenal of robust compounds with ideal properties for a drug candidate (e.g., easy availability and straightforward synthesis, appreciable water solubility, water stability and amphiphilicity), and the wide opportunity for structural variability offered by the diiron core encourages further studies in the direction to find out optimal combinations of ligands and substituents for the development of potential pharmaceuticals deserving more advanced biological evaluation.  
\begin{table}
\begin{tabular}{c c c c c} \hline \hline
**Comp.** & **A2780** & **A2780 cisR** & **A549** & **BxPC-3** \\ \hline
**2a** & _0.50 \(\pm\) 0.06_ & _1.2 \(\pm\) 0.2_ & 43 \(\pm\) 4 & 11.5 \(\pm\) 1.4 \\
**2a** & 5.3 \(\pm\) 1.2 (*) & 25 \(\pm\) 2 (*) & & \\
**2b** & _0.90 \(\pm\) 0.06_ & _4.0 \(\pm\) 0.3_ & \textgreater{}100 & \textgreater{}100 \\
**2c** & 35 \(\pm\) 3 & _86 \(\pm\) 7_ & \textgreater{}100 & \textgreater{}100 \\
**2d** & _2.9 \(\pm\) 0.2_ & _9.3 \(\pm\) 0.7_ & \textgreater{}100 & \textgreater{}2\(\pm\) 2 \\
**2e** & _1.8 \(\pm\) 0.2_ & _7.5 \(\pm\) 0.3_ & \textgreater{}100 & \textgreater{}100 \\
**3a** & _16 \(\pm\) 2_ & _26 \(\pm\) 3_ & & \\
**3a** & 37 \(\pm\) 2 (*) & 86 \(\pm\) 4 (*) & & \\
**4a** & 25.9 \(\pm\) 1.6 & 29 \(\pm\) 3 & & \\
**4b** & 37 \(\pm\) 3 & 42 \(\pm\) 6 & & \\
**4c** & 39 \(\pm\) 2 & 50 \(\pm\) 6 & & \\
**5a** & 64 \(\pm\) 4 & \textgreater{}100 & & \\
**5b** & \textgreater{}100 & \textgreater{}100 & & \\ cisplatin & 19.0 \(\pm\) 1.1 (*) & 71 \(\pm\) 3 (*) & & \\ cisplatin & 0.40 \(\pm\) 0.07 & 26 \(\pm\) 3 & 9.5 \(\pm\) 0.6 & 4.6 \(\pm\) 0.4 \\ \hline \hline \end{tabular}
\end{table}
Table 1: IC\({}_{50}\) values (uM) determined for iron complexes and cisplatin on cell lines after 72 h exposure, unless otherwise specified. Values are given as the mean \(\pm\) SD. Italic: previously reported data from ref. [20]. (*) Exposure time: 24 h.