The adrenal specific toxicant mitotane directly interacts with lipid membranes and alters membrane properties depending on lipid composition.

摘要: Mitotane (o,p'.-DDD) is an orphan drug approved for the treatment of adrenocortical carcinoma. The mechanisms, which are responsible this activity drug, not completely understood. It can be hypothesized that impact mitotane mediated by interaction with cellular membranes. However, (lipid) membranes has yet been investigated in detail. Here, we characterized and its main metabolite o,p'-dichlorodiphenyldichloroacetic acid (o,p'-DDA) lipid applying a variety biophysical approaches nuclear magnetic resonance, electron spin fluorescence spectroscopy. We found o,p'-DDA bind to inserting into lipid-water interface bilayer. but directly causes disturbance bilayer structure leading increased permeability membrane polar molecules. induced alterations integrity required presence phosphatidylethanolamine and/or cholesterol. Collectively, our data first time characterize on dynamics, may contribute better understanding specific effects side effects.