Structural correlations of choline acetyltransferase inhibitors: trans-N-(carboxymethyl)-4-(beta-1-naphthylvinyl)pyridinium bromide and cis-N-(2-aminoethyl)-4-(beta-1-naphthylvinyl)-3-methylpyridinium bromide hydrobromide.
This paper correlates the X-ray structures of two 4-(beta-1-naphthylvinyl)pyridine analogues (one cis and one trans) with chemical and biological activity data for this class of cholineacetylase inhibitors. Our results suggest that one of the two proposed mechanisms for inhibition by this class of compounds better describes their efficacy. Previous arguments about coplanarity of the aromatic rings and nucleophilicty across the vinyl linkage need to be modified. Quantum calculations are also included and substantiate previous suggestions about the charge distribution across the vinyl linkages. An alternate new mechanism of inhibition is proposed to encompass the published data and more recent results discussed in this paper.
D055598:Chemical Phenomena; D002621:Chemistry; D002795:Choline O-Acetyltransferase / Q000037:antagonists & inhibitors*; D003545:Cysteine; D008958:Models, Molecular; D009286:Naphthylvinylpyridine / Q000031:analogs & derivatives / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D011789:Quantum Theory; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds; D013455:Sulfur; D014961:X-Ray Diffraction
D011725:Pyridines; D013438:Sulfhydryl Compounds; D009286:Naphthylvinylpyridine; D013455:Sulfur; C041847:N-(carboxymethyl)-4-(beta-1-naphthylvinyl)pyridinium; C041848:N-(2-aminoethyl)-4-(beta-1-naphthylvinyl)-3-methylpyridinium; D002795:Choline O-Acetyltransferase; D003545:Cysteine; C007638:ethanethiol