STRUCTURAL EFFECTS OF THE AU(I) DRUG AURANOFIN ON CELL MEMBRANES AND MOLECULAR MODELS

Auranofin is a gold compound that is widely used for the treatment of rheumatoid arthritis. It is a monomeric linear complex with triethylphosphine and thiolate moieties bounded to an Au(I) center. Gold compounds are well known for their neurological and nephrotoxic implications. However, haematological toxicity is one of the most serious toxic and less studied effects. The lack of information on these aspects of auranofin prompted us to study the structural effects induced on cell membranes, particularly that of human erythrocytes. Auranofin was incubated with intact erythrocytes and molecular models of the erythrocyte membrane. The latter consisted of multibilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), phospholipids classes located in the outer and inner monolayers of the human erythrocyte membrane, respectively. This report presents evidence in order that auranofin interacts with red cell membranes as follows: a) in scanning electron microscopy studies on human erythrocytes it was observed that auranofin induced shape changes; b) X-ray diffraction studies showed that auranofin induced increasing structural perturbation to DMPC and to a lower extent to DMPE bilayers. Additional experiments were performed in human neuroblastoma cells SH-SY5Y. A statistically significant decrease of cell viability was observed.