1.-2′-Hydroxy-5′-methyl-3′-nitrochalcone: a novel chalcone with antinociceptive effects.

HIGGS J; WASOWSKI C; COLETTIS N; MARDER M

Mar del Plata

Congreso; XXX Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias.; 2015

Sociedad Argentina de Investigación en Neurociencias.

Chalcones (1,3-diaryl-2-propen-1-ones) belong to the flavonoid family.Chemically, they consist of open-chain flavonoids in which the twoaromatic rings are linked by a three-carbon α,β-unsaturated carbonylsystem. Chalcones have been reported to possess many pharmacologicalactivities, including anti-inflammatory, antimicrobial, antifungal,antioxidant, cytotoxic, antitumor and anticancer actions.The aim of this work was to synthesize, by aldol condensation, aseries of chalcones and evaluate their potential effect on the CentralNervous System (CNS). The binding capacity of these compounds toreceptors present in synaptosomal membranes of rat brain related toanxiety disorders, depression and pain was evaluated by displacementof labeled specific ligands: [3 H] FNZ (binding site forbenzodiazepines, in the GABAA receptor), [3H] 8-OH-DPAT (serotonin5-HT1A) and [3H] DAMGO (µ-opioid). One of the most active compound inthe binding inhibition of [3H] DAMGO, was5?-methyl-2?-hydroxy-3?-nitrochalcone, which presented a Ki value of13.5± 6.9 µM. In acute chemical and thermal models of nociception inmice, it exerted antinociceptive action without showing sedative,anxiolytic, antidepressant and motor incoordination effects. Blockadein vivo assays revealed that µ opioid receptors are involved in itsmechanism of action.