Cytotoxic triosmium carbonyl clusters : are proteins the target?

Abstract

The interaction of the cytotoxic triosmium carbonyl cluster Os3(CO)10(NCMe)2, 1 with different amino acids and oligopeptides was examined with regard to its selectivity towards the different residues. It was found that 1 was reactive to cysteine, glutamic acid, aspartic acid, glutamine and asparagine, with the propensity for reaction following the order: thiol > carboxylic acid > amide. This was found to be the case for the C, N–protected amino acids, as well as tri– and pentapeptides. Any steric effect from neighboring amino acids appears to be insignificant.

The triosmium carbonyl clusters Os3(CO)10(μ-H)(μ-OH), 3 and Os3(CO)10(μ-H)(μ-Cl), 6 were found to exhibit cell proliferative activity. Cluster 3 exhibited comparable cytotoxicity to Tamoxifen against both ER+ and ER– breast cancers. The mode of action of both clusters was determined to be the induction of apoptosis, but their biological target appeared to be different from that of 1.