2-hydroxy-5-methyl-3-nitrochalcone: a novel chalcone with antinociceptive effects

JOSEFINA HIGGS; CRISTINA WASOWSKI; NATALIA COLETTIS; MARIEL MARDER

Mar del Plata

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

2′-Hydroxy-5′-methyl-3′-nitrochalcone:a novel chalcone with antinociceptive effectsChalcones (1,3-diaryl-2-propen-1-ones) belong to the flavonoid family.Chemically, they consist of open-chain flavonoids in which the two aromaticrings are linked by a three-carbon α,β-unsaturated carbonyl system. Chalconeshave been reported to possess many pharmacological activities, includinganti-inflammatory, antimicrobial, antifungal, antioxidant, cytotoxic, antitumorand anticancer actions. The aim of this work was to synthesize, by aldolcondensation, a series of chalconesand evaluate their potential effect onthe Central Nervous System (CNS). Thebinding capacity of these compounds to receptors present insynaptosomal membranes of rat brain related to anxietydisorders, depression and painwas evaluated by displacement of labeled specific ligands: [3 H] FNZ (bindingsite for benzodiazepines, in the GABAA receptor), [3H] 8-OH-DPAT (serotonin5-HT1A)and [3H] DAMGO (µ-opioid). One of the most active compound in the binding inhibitionof [3H] DAMGO, was 5?-methyl-2?-hydroxy-3?-nitrochalcone, whichpresented a Ki value of 13.5± 6.9 µM. In acute chemical and thermal models ofnociception in mice, it exerted antinociceptive action without showing sedative,anxiolytic, antidepressant and motor incoordination effects. Blockade in vivo assays revealed that µ opioidreceptors are involved in its mechanism of action.