a Programa de Pós-Gradução em Química (PPGQ) , Universidade Federal Rural do Rio de Janeiro , Rio de Janeiro , Brazil.
b Laboratório de Diversidade Molecular e Química Medicinal (LaDMol-QM, Molecular Diversity and Medicinal Chemistry Laboratory), Departament of Chemistry , Universidade Federal Rural do Rio de Janeiro , Rio de Janeiro , Brazil.
J Enzyme Inhib Med Chem. 2019 Dec;34(1):631-637. doi: 10.1080/14756366.2019.1571270.
A series of 3-substituted-7-aminoalcoxy-coumarin was designed and evaluated as cholinesterase inhibitors and antioxidants. All compounds were effective in inhibiting AChE with potencies in the nanomolar range. The 3-(4-(dimethylamino)phenyl)-7-aminoethoxy-coumarin (6a) was considered a hit, showing good AChE inhibition potency (IC = 20 nM) and selectivity (IC BuChE/AChE = 354), quite similar to the reference drug donepezil (IC = 6 nM; IC BuChE/AChE = 365), also presenting antioxidant properties, low citotoxicity and good-predicted ADMET properties. The mode of action (mixed-type) and SAR analysis for this series of compounds were described by means of kinetic and molecular modeling evaluations.
设计并评价了一系列 3-取代-7-烷氧基香豆素作为胆碱酯酶抑制剂和抗氧化剂。所有化合物均能有效抑制 AChE，其效力在纳摩尔范围内。3-(4-(二甲基氨基)苯基)-7-乙氧基香豆素（6a）被认为是一个有效化合物，具有良好的 AChE 抑制活性（IC=20nM）和选择性（IC BuChE/AChE=354），与参考药物多奈哌齐（IC=6nM；IC BuChE/AChE=365）相当，同时还具有抗氧化、低细胞毒性和良好的预测 ADMET 特性。通过动力学和分子建模评估，描述了该系列化合物的作用模式（混合型）和 SAR 分析。
