Spatial structure of atorvastatin and its complex with model membrane in solution studied by NMR and theoretical calculations

Atorvastatin is a drug of the statin group which possesses the ability to decrease low-density lipoprotein cholesterol level by the competitive inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase. There is a hypothesis that pharmacological properties of statins depend on their location in the cell membrane. Intermolecular complex of atorvastatin with dodecylphosphocholine (DPC) micelle was investigated by NMR and computational methods. The results of NMR experiments showed that atorvastatin forms molecular complex with model membrane in solution by penetrating a space between hydrocarbon chains of the DPC micelle, Analysis of obtained data in comparison with previously reported results for simvastatin, pravastatin, fluvastatin and cerivastatin showed that locations of statins in model membranes correlate with their pharmacological features, such as efficacy and risk of rhabdomyolysis. (C) 2018 Elsevier B.V. All rights reserved.