Chaturvedi A K, Rowell P P, Sastry B V
J Pharm Sci. 1978 May;67(5):657-60. doi: 10.1002/jps.2600670522.
Seven keto analogs of acetylcholine were synthesized and evaluated as inhibitors of human placental choline placental choline acetyltransferase. Their potencies for inhibition of horse serum cholinesterase and stimulation of cholinergic receptors in the longitudinal ileal muscle of the guinea pig were investigated. The most potent and selective inhibitor of choline acetyltransferase was (2-benzoylethyl)trimethylammonium chloride with an I50 of 3 X 10(-6) M. It exhibited considerably low activities at muscarinic and nicotinic receptors and cholinesterases. Its high potency for inhibiting choline acetyltransferase was atrributed to: (a) its cationic terminal, a site for an electron acceptor interaction; (b) an aryl moiety for hydrophobic and electron donor contributions; and (c) a positive charge on the carbon atom adjacent to the benzene ring due to the presence of the carbonyl group, which interacts with the nucleophilic residue on the enzyme.
合成了七种乙酰胆碱的酮类似物，并对其作为人胎盘胆碱乙酰转移酶抑制剂进行了评估。研究了它们对马血清胆碱酯酶的抑制能力以及对豚鼠纵行回肠肌胆碱能受体的刺激作用。胆碱乙酰转移酶最有效和选择性的抑制剂是（2-苯甲酰乙基）三甲基氯化铵，其半数抑制浓度为3×10⁻⁶M。它在毒蕈碱和烟碱受体以及胆碱酯酶上表现出相当低的活性。其对胆碱乙酰转移酶的高效抑制作用归因于：（a）其阳离子末端，一个电子受体相互作用的位点；（b）一个用于疏水和电子供体作用的芳基部分；以及（c）由于羰基的存在，苯环相邻碳原子上的正电荷，该正电荷与酶上的亲核残基相互作用。
