Ferrocene–Biotin Conjugates Targeting Cancer Cells: Synthesis, Interaction with Avidin, Cytotoxic Properties and the Crystal Structure of the Complex of Avidin with a Biotin–Linker–Ferrocene Conjugate

Abstract

Friedel–Crafts acylation of ferrocene with a biotin-derived carboxylic acid having 6-aminohexanoyl linkers attached to the biotin carboxylic group and with desthiobiotin afforded the corresponding ferrocene–biotin bioconjugates. These compounds as well as biotinyl ferrocenyl ketone exhibit high affinity for avidin. Their cytotoxicity against cancer cell lines having various levels of biotin receptors (SMVT) was measured and revealed that lines displaying high levels of SMVT (SW620) were the most susceptible. This suggests that biotin serves as a biological vector delivering cytotoxic ferrocenyl moieties to cancer cells. The crystal structure of the complex of avidin with a conjugate having two linker units between biotin and ferrocene was determined and revealed stabilization of several different conformations of the ligand within the protein binding pocket.