Synthesis of poison-frog alkaloids 233A, 235U, and 251AA and their inhibitory effects on neuronal nicotinic acetylcholine receptors

Bioorg Med Chem Lett. 2007 Nov 1;17(21):5872-5. doi: 10.1016/j.bmcl.2007.08.045. Epub 2007 Aug 26.

Abstract

We previously reported that the synthetic quinolizidine 1-epi-207I is a relatively selective blocker of alpha7 nicotinic acetylcholine receptors. We now synthesized the analogous poison frog alkaloids 233A, 235U, and 251AA, and investigated the biological activities at two major types of neuronal nicotinic receptors. Electrophysiological study showed that the alkaloid 233A blocked alpha7 and alpha4beta2 currents with similar potencies. Alkaloids 235U and 251AA also showed similar potencies for blockade of alpha7 and alpha4beta2 currents. Thus, based on these studies, it would appear that C4 substituents greater in length than the allyl of 1-epi-207I reduce alpha7-potency without affecting alpha4beta2-potency.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemical synthesis*
  • Alkaloids / pharmacology*
  • Animals
  • Anura
  • Chromatography, Gas
  • Neurons / drug effects*
  • Receptors, Nicotinic / drug effects*
  • Xenopus laevis

Substances

  • Alkaloids
  • Receptors, Nicotinic