gms | German Medical Science

Propargylhexacarbonyldicobalt complexes with fructopyranose ligands were prepared and investigated for cytotoxicity and cellular uptake using the MCF-7 human breast cancer cell line. Furthermore, their influence on eicosanoid metabolism was evaluated. The aim was the development of new cytotoxic cyclooxygenase (COX)/ lipooxygenase (LOX) inhibitors which combine essential structural features of the two metal based: drugs auranofin, a gold-glucose complex, and Co-ASS, a propargylhexacarbonyldicobalt derivative of acetylsalicylic acid. Both compounds showed antiproliferative effects in tumor models in previous studies. This might be the result of the inhibition of the COX and LOX enzymes which is discussed as a promising strategy for the design of new cytostatics. The accomplished studies showed that the antiproliferative effects of the target compounds depended on the number of protecting groups and correlated with the cellular uptake. The ability of the fructopyranose complexes and the references auranofin and Co-ASS to inhibit COX-1 and 12-LOX product formation was determined using human platelets by quantification of the eicosanoids 12-HHT (COX-1 product) and 12-HETE (12-LOX product). Co-ASS was an efficient COX-1 inhibitor without LOX inhibitory activity and auranofin inhibited both COX-1 and 12-LOX eicosanoid production. However, the target compounds showed only minor effects concerning COX-1 and 12-LOX. These results indicate that inhibition of COX-1 and 12-LOX may correspond to the pharmacological effect of Co-ASS and auranofin but not of the cobalt-alkyne fructopyranose derivatives.