1,3-diphenylpropan-1-ones as allosteric modulators of α7 nACh receptors with analgesic and antioxidant properties-Reference-Cited by-同舟云学术

1,3-diphenylpropan-1-ones as allosteric modulators of α7 nACh receptors with analgesic and antioxidant properties

Published:2016-05 Issue:7 Volume:8 Page:731-749
ISSN:1756-8919
Container-title:Future Medicinal Chemistry
language:en
Short-container-title:Future Medicinal Chemistry

Author:

Criado Manuel¹,Balsera Beatriz²,Mulet José¹,Sala Salvador¹,Sala Francisco¹,de la Torre-Martínez Roberto³,Fernández-Carvajal Asia³,Ferrer-Montiel Antonio³,Moreno-Fernández Silvia⁴,Miguel Marta⁴,Pérez de Vega María Jesús²,González-Muñiz Rosario²

Affiliation:

1. Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, 03050 Sant Joan d'Alacant, Spain

2. Instituto de Química Médica, IQM-CSIC, Juan de la Cierva 3, 28006 Madrid, Spain

3. Instituto de Biología Molecular y Celular, Universidad Miguel Hernández, Avenida de la Universidad s/n, 03202 Elche (Alicante), Spain

4. Instituto de Investigación en Ciencias de la Alimentación (CSIC-UAM, CEI+UAM), C/Nicolás Cabrera 9, 28049 Madrid, Spain

Abstract

Nicotine acethylcholine receptors (nAChRs) play critical roles in cognitive processes, neuroprotection and inflammation. Results: 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. Conclusion: 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.

Publisher

Future Science Ltd

Subject

Drug Discovery,Pharmacology,Molecular Medicine

Link

http://www.future-science.com/doi/pdf/10.4155/fmc-2015-0001

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