title: Synthesis and Pharmacological Evaluation of DHβE Analogues as Neuronal Nicotinic Acetylcholine Receptor Antagonists.
abstract: Dihydro-β-erythroidine (DHβE) is a member of the Erythrina family of alkaloids and a potent competitive antagonist of the α4β2-subtype of the nicotinic acetylcholine receptors (nAChRs). Guided by an X-ray structure of DHβE in complex with an ACh binding protein, we detail the design, synthesis, and pharmacological characterization of a series of DHβE analogues in which two of the four rings in the natural product has been excluded. We found that the direct analogue of DHβE maintains affinity for the α4β2-subtype, but further modifications of the simplified analogues were detrimental to their activities on the nAChRs.
authors: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen , Universitetsparken 2, 2100 Copenhagen, Denmark.
authors: Tue Heesgaard
authors: TH
authors: Jepsen
authors: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen , Universitetsparken 2, 2100 Copenhagen, Denmark.
authors: Anders A
authors: AA
authors: Jensen
authors: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen , Universitetsparken 2, 2100 Copenhagen, Denmark.
authors: Mads Henrik
authors: MH
authors: Lund
authors: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen , Universitetsparken 2, 2100 Copenhagen, Denmark.
authors: Emil
authors: E
authors: Glibstrup
authors: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen , Universitetsparken 2, 2100 Copenhagen, Denmark.
authors: Jesper Langgaard
authors: JL
authors: Kristensen
keywords: Dihydro-β-erythroidine; antagonist; nAChR; natural product analogues