新型 2H-色烯-3-甲酰胺衍生物：设计、合成及作为 hMAO 抑制剂的应用。
New 2H-chromene-3-carboxamide derivatives: design, synthesis and use as inhibitors of hMAO.
机构信息
School of Pharmacy, Anhui Medical University, Hefei 230032, PR China.
Key Laboratory of Green Pesticide and Agriculture Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, PR China.
出版信息
Eur J Med Chem. 2014 Jun 10;80:278-84. doi: 10.1016/j.ejmech.2014.04.060. Epub 2014 Apr 23.
A series new 2H-chromene-3-carboxamide derivatives 4a-4t were synthesized and evaluated as monoamine oxidase A and B (MAO-A and MAO-B) inhibitors. Among them, compound 4d (IC50 = 0.93 μM, IC(50 iproniazid) = 7.80 μM) showed the most activity and higher MAO-B selectivity (64.5-fold vs. 1-fold) with respect to the MAO-A isoform. The active compound 4d was also docked into the hMAO-B complex structure active site to determine the probable binding model. The results indicated that conserved residue CYSA 172 was important for ligand binding via hydrogen bond interaction, Pi-Pi interaction was found between the benzene-ring of compound 4d and residue ILEA 199.
一系列新型 2H-色烯-3-甲酰胺衍生物 4a-4t 被合成并评估为单胺氧化酶 A 和 B（MAO-A 和 MAO-B）抑制剂。其中，化合物 4d（IC50 = 0.93 μM，IC（50 异丙烟肼）= 7.80 μM）表现出最强的活性和更高的 MAO-B 选择性（相对于 MAO-A 同工酶为 64.5 倍）。活性化合物 4d 也被对接入 hMAO-B 复合物结构的活性位点，以确定可能的结合模型。结果表明，保守残基 CYSA 172 通过氢键相互作用对配体结合很重要，在化合物 4d 的苯环和残基 ILEA 199 之间发现了 Pi-Pi 相互作用。
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