Effective Antitumor Candidates Based upon Ferrocenylseleno-Dopamine Derivatives: Growth Inhibition by Induction Cell Apoptosis and Antivascular Effects

One ferrocenyl-dopamine (L1) and four ferrocenylseleno-dopamine derivatives (L2-L5) were designed and prepared with different structural parameters, such as chalcogen atoms, cycle, and semirigidity. The best in vitro anticancer activity occurred with 1,5-diselena[8]ferrocenophane L5, which inhibited cancer cell growth at the lowest micromolar concentrations. The biological studies showed that L5 arrested the cell cycle in G1 phase and induced apoptosis by activating caspase 3/9, also inhibiting endothelial cell (HUVECs) formation. It exhibited better in vivo antitumor activity in mice bearing HepG2 tumor xenograft in comparison to free dopamine. The results suggest that the excellent biological activities can be attributed to the synergetic effect of the ferrocenophane, chalcogen atom, and catechol group.