ATP-hydrolyzing, DNA-damaging and cytotoxic activities of peptide-targeted cobalt(III) complex with diethylentriamine

Abstract

Coordination complexes of cobalt represent a potential alternative to anticancer platinum-derived drugs owing to multiple activities and better toxicity profile. This work is aimed at generation of novel cobalt complexes based on peptide-conjugated diethylentriamine (Dien) ligand. Dien derivatives including SPPS-compliant Boc-protected N,N′-di(2-aminoethyl)glycine and its conjugate with RGD peptide derivative (compound 6) were synthesized. Cobalt(III) complexes of Dien and 6 were obtained and characterized. Both complexes exhibited comparable ATP-depleting activity in solution and in PC-3 and OVCAR-4 cancer cells. The complex of 6 showed profoundly increased prooxidant, cytotoxic, and apoptotic in vitro effects compared to the non-targeted counterpart. Both complexes bound DNA and caused its significant damage in the presence of glutathione or hydrogen peroxide. These results provide an important background for development of bioactive cobalt complexes conjugated with biospecific oligopeptides.