2. Academic Validation
  3. 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

  • J Med Chem. 2018 Aug 9;61(15):6937-6943. doi: 10.1021/acs.jmedchem.8b00848.
Óscar M Bautista-Aguilera 1,  Josiane Budni 2,  Francielle Mina 2,  Eduarda Behenck Medeiros 2,  Winnie Deuther-Conrad 3,  José M Entrena 4,  Ignacio Moraleda 5,  Isabel Iriepa 5,  Francisco López-Muñoz 6 7,  José Marco-Contelles 1
Affiliations

Affiliations

  • 1 Laboratory of Medicinal Chemistry, IQOG, CSIC , C/Juan de la Cierva 3 , 28006 Madrid , Spain.
  • 2 Laboratório de Neurologia Experimental , Universidade do Extremo Sul Catarinense , Av. Universitária , 1105 Criciúma , Brazil.
  • 3 Department of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research , Helmholtz-Zentrum Dresden-Rossendorf , 04318 Leipzig , Germany.
  • 4 Animal Behavior Research Unit, Scientific Instrumentation Center , University of Granada , Parque Tecnológico de Ciencias de la Salud , 18100 Armilla , Granada , Spain.
  • 5 Departamento de Química Orgánica and Química Inorgánica , Universidad de Alcalá , Ctra. Madrid-Barcelona, Km. 33,6 , 28871 Madrid , Spain.
  • 6 Faculty of Health , Camilo José Cela University , 28692 Villanueva de la Cañada, Madrid , Spain.
  • 7 Neuropsychopharmacology Unit , "Hospital 12 de Octubre" Research Institute , 28041 Madrid , Spain.
PMID: 29969030 DOI: 10.1021/acs.jmedchem.8b00848
Abstract

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 S1R 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 Aβ1-42 in the radial maze assay in an in vivo Alzheimer's disease test, comparing very favorably with donepezil.

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