Design and synthesis of tacrine-ferulic acid hybrids as multi-potent anti-Alzheimer drug candidates
Design and synthesis of tacrine-ferulic acid hybrids as multi-potent anti-Alzheimer drug candidates
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DOI：
10.1016/j.bmcl.2008.03.073
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发表时间：
2008-05-01
影响因子：
2.7
通讯作者：
Decker, Michael
中科院分区：
文献类型：
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作者：
Fang, Lei;Kraus, Birgit;Decker, Michael
设计并合成了5个他克林-阿魏酸杂化化合物(6a-e)作为多效抗阿尔茨海默病候选药物。所有目标化合物都具有更好的乙酰胆碱酯酶抑制活性和与他克林相当的丁酰胆碱酯酶抑制活性。有趣的是，6d对乙酰胆碱酯酶表现出可逆的非竞争性抑制作用，表明与外周阴离子位点相互作用，而对丁基胆碱酯酶表现出可逆的竞争性抑制作用。抗氧化剂研究表明，与Trolox相比，四种目标化合物具有更高的吸收活性氧物种的能力。(C)2008爱思唯尔有限公司。保留所有权利。
Five tacrine-ferulic acid hybrids (6a-e) were designed and synthesized as multi-potent anti-Alzheimer drug candidates. All target compounds have better acetylcholinesterase inhibitory activity and comparable butyrylcholinesterase inhibitory activity in relation to tacrine. Interestingly, 6d showed a reversible and non-competitive inhibitory action for acetylcholinesterase indicating interaction with the peripheral anionic site, whereas a reversible but competitive inhibitory action for butyrylcholinesterase. The antioxidant study revealed that four target compounds have, compared to Trolox, high ability to absorb reactive oxygen species. (C) 2008 Elsevier Ltd. All rights reserved.