3-(4-Hydroxybenzylidene)anabaseine: High-affinity ligand for Periplaneta americana nicotinic acetylcholine receptors

Abstract

3-Benzylideneanabaseine analogues with electron-donating ortho- and/or para-substituents on the benzene ring were synthesized. The affinity of the analogues for nicotinic acetylcholine receptors in the nerve cord of the American cockroach (Periplaneta americana L.) was determined by the radioligand binding assay using [³H]epibatidine. Among the compounds tested, 3-(4-hydroxybenzylidene)anabaseine (6) displayed the highest potency, with IC₅₀ values of 3.6 nM. In contrast, 3-(4-methoxybenzylidene)anabaseine (5) showed the lowest potency (IC₅₀=188.3 nM). Compound 6 was found to have 52-fold higher affinity than 5. 3-(2,4-Dimethoxybenzylidene)anabaseine (1) and 3-(2-hydroxy-4-methoxybenzylidene)anabaseine (2) showed higher potency than 5, with IC₅₀ values of 41.6 and 63.5 nM, respectively. Compound 6 might prove to be a good lead compound for the development of novel insecticides.