title: 1,3-diphenylpropan-1-ones as allosteric modulators of α7 nACh receptors with analgesic and antioxidant properties.
abstract: Nicotine acethylcholine receptors (nAChRs) play critical roles in cognitive processes, neuroprotection and inflammation.
  
  
  
  According to their substituents, 1,3-diphenylpropan-1-one derivatives act as α7 nAChRs negative allosteric modulators (NAM, OMe) or Type I positive allosteric modulators (PAMs, OH). Compounds 7 and 31 were the most effective (989 and 666% enhancement of ACh-induced currents) and potent (EC50: 12.9 and 6.85 μM) PAMs. They exhibited strong radical scavenging values. Compound 31, selective over other neuronal nAChR subtypes and with acceptable pharmacokinetic profile, showed antinociceptive effects in a model of inflammatory pain.
  
  
  
  Compound 31 is a novel, potent and selective α7 nAChR PAM, displaying antioxidant and analgesic activities. The 1,3-diphenylpropan-1-one scaffold could be the base toward more advanced type I PAMs for the treatment of nAChR-mediated diseases.
authors.affiliation: Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, 03050 Sant Joan d'Alacant, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Criado
authors.affiliation: Instituto de Química Médica, IQM-CSIC, Juan de la Cierva 3, 28006 Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Balsera
authors.affiliation: Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, 03050 Sant Joan d'Alacant, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Mulet
authors.affiliation: Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, 03050 Sant Joan d'Alacant, Spain.
authors.forename: Salvador
authors.initials: S
authors.lastname: Sala
authors.affiliation: Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, 03050 Sant Joan d'Alacant, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Sala
authors.affiliation: Instituto de Biología Molecular y Celular, Universidad Miguel Hernández, Avenida de la Universidad s/n, 03202 Elche (Alicante), Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: de la Torre-Martínez
authors.affiliation: Instituto de Biología Molecular y Celular, Universidad Miguel Hernández, Avenida de la Universidad s/n, 03202 Elche (Alicante), Spain.
authors.forename: Asia
authors.initials: A
authors.lastname: Fernández-Carvajal
authors.affiliation: Instituto de Biología Molecular y Celular, Universidad Miguel Hernández, Avenida de la Universidad s/n, 03202 Elche (Alicante), Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Ferrer-Montiel
authors.affiliation: Instituto de Investigación en Ciencias de la Alimentación (CSIC-UAM, CEI+UAM), C/Nicolás Cabrera 9, 28049 Madrid, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Moreno-Fernández
authors.affiliation: Instituto de Investigación en Ciencias de la Alimentación (CSIC-UAM, CEI+UAM), C/Nicolás Cabrera 9, 28049 Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Miguel
authors.affiliation: Instituto de Química Médica, IQM-CSIC, Juan de la Cierva 3, 28006 Madrid, Spain.
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Pérez de Vega
authors.affiliation: Instituto de Química Médica, IQM-CSIC, Juan de la Cierva 3, 28006 Madrid, Spain.
authors.forename: Rosario
authors.initials: R
authors.lastname: González-Muñiz
mesh_terms: D000494:Allosteric Regulation; D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D015870:Gene Expression; D006801:Humans; D011407:Propane / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000700:Analgesics; D000975:Antioxidants; D064569:alpha7 Nicotinic Acetylcholine Receptor; D011407:Propane; C014513:1,3-diphenylpropane
keywords: antioxidant; inflammation; pain; positive allosteric modulator; α7 nAChR