Contilisant, a Tetratarget Small Molecule for Alzheimer's Disease Therapy Combining Cholinesterase, Monoamine Oxidase Inhibition, and H3R Antagonism with S1R Agonism Profile
Contilisant, a Tetratarget Small Molecule for Alzheimer's Disease Therapy Combining Cholinesterase, Monoamine Oxidase Inhibition, and H3R Antagonism with S1R Agonism Profile
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DOI：
10.1021/acs.jmedchem.8b00848
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发表时间：
2018-08-09
影响因子：
7.3
通讯作者：
Marco-Contelles, Jose
中科院分区：
文献类型：
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作者：
Bautista-Aguilera, Oscar M.;Budni, Josiane;Marco-Contelles, Jose
Contilisant是一种渗透性、抗氧化剂和神经保护剂，对H3 R显示出高nM亲和力，对单胺氧化酶和胆碱酯酶具有优异的抑制作用，是一种基于结合亲和力和功能实验的纳摩尔范围内的亲和性和选择性SIR激动剂，该结果通过分子建模得到证实。此外，与多奈哌齐相比，contilisant在体内阿尔茨海默病测试中的径向迷宫测定中显著恢复由A β（1-42）诱导的认知缺陷。
Contilisant, a permeable, antioxidant, and neuroprotectant agent, showing high nM affinity at H3R and excellent inhibition of the monoamine oxidases and cholinesterases, is an affine and selective SIR agonist in the nanomolar range, based on the binding affinity and functional experiment, a result confirmed by molecular modeling. In addition, contilisant significantly restores the cognitive deficit induced by A beta(1-42) in the radial maze assay in an in vivo Alzheimer's disease test, comparing very favorably with donepezil.