title: Models for the binding of amiodarone to the thyroid hormone receptor.
abstract: The antiarrhythmic drug amiodarone has recently been characterized as the first known thyroid hormone antagonist. Its mode of interaction with the thyroid hormone receptor is therefore of interest. A computational analysis of the conformational flexibility of amiodarone using molecular mechanics and the semiempirical molecular orbital method AM1 has been performed. The molecular mechanics studies show that the low-energy conformations of the benzoylbenzofuran portion of amiodarone can be grouped into 4 distinct classes, while the diethylaminoethoxy side chain is extremely flexible. Conformers representative of the 4 low-energy classes were fitted to an extended thyroid hormone receptor model. Four independent modes in which amiodarone could bind to the thyroid hormone receptor site were evaluated.
authors.affiliation: School of Pharmaceutical Chemistry, Victorian College of Pharmacy Ltd., Parkville, Australia.
authors.forename: D K
authors.initials: DK
authors.lastname: Chalmers
authors.forename: S L
authors.initials: SL
authors.lastname: Munro
authors.forename: M N
authors.initials: MN
authors.lastname: Iskander
authors.forename: D J
authors.initials: DJ
authors.lastname: Craik
mesh_terms: D000638:Amiodarone / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D008958:Models, Molecular; D008968:Molecular Conformation; D011988:Receptors, Thyroid Hormone / Q000737:chemistry / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D011988:Receptors, Thyroid Hormone; D000638:Amiodarone