title: A conformational analysis study of the interaction of amiodarone and cholesterol with lysophosphatidylcholine.
abstract: The spatial configuration of amiodarone (in both its protonated and neutral forms) and a hydroxylated analog was studied using conformational analysis in a simulated membrane-water environment. The three compounds and cholesterol were studied as isolated molecules and in interaction with lysophosphatidylcholine. The association of the molecules with lysophosphatidylcholine was further characterized by incorporation in a phosphatidylcholine matrix. Calculation of the mean interaction energy, the surface charge density and the hydrophilic and hydrophobic mean molecular areas showed that the protonated form of amiodarone, and to a lesser extent cholesterol form a stable association with lysophosphatidylcholine. This association was further stabilized when incorporated into a phosphatidylcholine matrix so that the mean interaction energy increased to -96.1 kJ/mol (i.e. 60% higher than the mean lipid-lipid energy of interaction). Lysophosphatidylcholine was shown to possess a cone-shaped structure whilst amiodarone was shown to be in the form of an inverted cone. This association of the two cones forms a stable cylindrical structure.
authors.affiliation: Sanofi-Labaz Research Centre, Brussels, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Chatelain
authors.forename: R
authors.initials: R
authors.lastname: Brasseur
mesh_terms: D000638:Amiodarone; D002784:Cholesterol; D004347:Drug Interactions; D008244:Lysophosphatidylcholines; D008958:Models, Molecular; D008968:Molecular Conformation; D013816:Thermodynamics
chemical_list: D008244:Lysophosphatidylcholines; D002784:Cholesterol; D000638:Amiodarone