Synthesis, molecular modeling and preliminary anticancer evaluation of 2-ferrocenylbenzimidazole metallofragments

Abstract The synthesis of 2-ferrocenylbenzimidazole metallofragments, with varying substituents in the 5-position of a benzimidazole scaffold is described. This strategy involves linking bioactive multinuclear compounds with known pharmacophores with the potential to interact with protein targets. To further understand the interactions of multinuclear complexes with proteins, in silico simulations were performed by employing protein models of common cancer therapeutic targets to predict their affinity to bind to these proteins. The trinuclear complexes show higher affinities and superior binding energies over monomeric congeners. The synthesized compounds were screened for their cytotoxic activity against two breast cancer cell lines, and selected compounds showed moderate activity. These results suggest that the conjugation of the ferrocene moiety to the benzimidazole motif presents a valuable strategy in the design of organometallic compounds for anticancer chemotherapy.