A series of new pyrrole derivatives have been synthesized and evaluated for their monoamine oxidase (MAO) A and B inhibitory activity and selectivity. N-Methyl,N-(benzyl),N-(pyrrol-2-ylmethyl)amine (7) and N-(2-benzyl),N-(1-methylpyrrol-2-ylmethyl)amine (18) were the most selective MAO-B (7, SI = 0.0057) and MAO-A (18, SI = 12500) inhibitors, respectively. Docking and molecular dynamics simulations gave structural insights into the MAO-A and MAO-B selectivity. Compound 18 forms an H-bond with Gln215 through its protonated amino group into the MAO-A binding site. This H-bond is absent in the 7/MAO-A complex. In contrast, compound 7 places its phenyl ring into an aromatic cage of the MAO-B binding pocket, where it forms charge-transfer interactions. The slightly different binding pose of 18 into the MAO-B active site seems to be forced by a bulkier Tyr residue, which replaces a smaller Ile residue present in MAO-A.

中文翻译：

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单胺氧化酶的新型吡咯抑制剂：MAO-A和MAO-B选择性的合成，生物学评估和结构决定因素。

合成了一系列新的吡咯衍生物，并对其单胺氧化酶（MAO）A和B的抑制活性和选择性进行了评估。N-甲基，N-（苄基），N-（吡咯-2-基甲基）胺（7）和N-（2-苄基），N-（1-甲基吡咯-2-基甲基）胺（18）最多选择性MAO-B（7，SI = 0.0057）和MAO-A（18，SI = 12500）抑制剂。对接和分子动力学模拟提供了对MAO-A和MAO-B选择性的结构见解。化合物18通过其质子化的氨基与Gln215形成H键，进入MAO-A结合位点。7 / MAO-A复合物中不存在这种H键。相反，化合物7将其苯环放入MAO-B结合口袋的芳族笼中，在其中形成电荷转移相互作用。