Contilisant, a Tetratarget Small Molecule for Alzheimer's Disease Therapy Combining Cholinesterase, Monoamine Oxidase Inhibition, and H3R Antagonism with S1R Agonism Profile

被引：53

作者：

Bautista-Aguilera, Oscar M. ^{[1
]}

Budni, Josiane ^{[2
]}

Mina, Francielle ^{[2
]}

Medeiros, Eduarda Behenck ^{[2
]}

Deuther-Conrad, Winnie ^{[3
]}

Entrena, Jose M. ^{[4
]}

Moraleda, Ignacio ^{[5
]}

Iriepa, Isabel ^{[5
]}

Lopez-Munoz, Francisco ^{[6
,7
]}

Marco-Contelles, Jose ^{[1
]}

机构：

[1] CSIC, IQOG, Lab Med Chem, C Juan Cierva 3, E-28006 Madrid, Spain

[2] Univ Extremo Catarinense, Lab Neurol Expt, Av Univ 1105, Criciuma, Brazil

[3] Helmholtz Zentrum Dresden Rossendorf, Inst Radiopharmaceut Canc Res, Dept Neuroradiopharmaceut, D-04318 Leipzig, Germany

[4] Univ Granada, Sci Instrumentat Ctr, Anim Behav Res Unit, Parque Tecnol Ciencias Salud, Granada 18100, Spain

[5] Univ Alcala, Dept Quim Organ & Quim Inorgan, Km 33,6, Madrid 28871, Spain

[6] Camilo Jose Cela Univ, Fac Hlth, Madrid 28692, Spain

[7] Hosp 12 Octubre, Res Inst, Neuropsychopharmacol Unit, E-28041 Madrid, Spain

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2018年 / 61卷 / 15期

关键词：

H-3 RECEPTOR ANTAGONISTS; SIGMA(1) RECEPTOR; BIOLOGICAL EVALUATION; ACETYLCHOLINESTERASE INHIBITORS; IN-VITRO; LIGANDS; IDENTIFICATION; DERIVATIVES; POTENT; MEMORY;

D O I：

10.1021/acs.jmedchem.8b00848

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：6937 / 6943

页数：7

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