2. Academic Validation
  3. Synthesis and Pharmacological Evaluation of DHβE Analogues as Neuronal Nicotinic Acetylcholine Receptor Antagonists

Synthesis and Pharmacological Evaluation of DHβE Analogues as Neuronal Nicotinic Acetylcholine Receptor Antagonists

  • ACS Med Chem Lett. 2014 May 20;5(7):766-70. doi: 10.1021/ml500094c.
Tue Heesgaard Jepsen 1,  Anders A Jensen 1,  Mads Henrik Lund 1,  Emil Glibstrup 1,  Jesper Langgaard Kristensen 1
Affiliations

Affiliation

  • 1 Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen , Universitetsparken 2, 2100 Copenhagen, Denmark.
PMID: 25050162 DOI: 10.1021/ml500094c
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.

Keywords

Dihydro-β-erythroidine; antagonist; nAChR; natural product analogues.

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