Evaluation of the Side Arm of (Naphthylvinyl)pyridinium Inhibitors of Choline Acetyltransferase

Article abstract of DOI:10.1021/jm00396a017

A number of quaternary salts of trans-4-(β-1-naphthylvinyl)pyridine (NVP) were synthesized and evaluated as inhibitors of the enzyme choline acetyltransferase (ChAT) and acetylcholinesterase (AChE).Structural variations in the side arm attashed to the pyridine nitrogen atom demonstrate that an inductive effect is small but significant for activity.Inhibition of ChAT by alkylated derivatives decreases when electron-withdrawing groups are placed in the side chain.Substitution of a methyl group on the pyridine ring only slightly affects activities toward ChAT and AChE.When the pyridinium moiety is replaced by an imidazolium ring, no ChAT inhibition was observed.The imidazolium compound, however, was a weak inhibitor of AChE.For design of affinity columns for purification of ChAT, the data also support the use of long chain alkylated amide derivatives of NVP.