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

J. HIGGS; C. WASOWSKI; N. COLETTIS; M. MARDER

Mar del Plata

Congreso; XXX Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias (SAN); 2015

Chalcones (1,3-diaryl-2-propen-1-ones) belong to the flavonoid family. Chemically, they consist of open-chain flavonoids in which the two aromatic rings are linked by a three-carbon alpha,beta-unsaturated carbonyl system. Chalcones have been reported to possess many pharmacological activities, including anti-inflammatory, antimicrobial, antifungal, antioxidant, cytotoxic, antitumor and anticancer actions. The aim of this work was to synthesize, by aldol condensation, a series of chalcones and evaluate their potential effect on the Central Nervous System (CNS). The binding capacity of these compounds to receptors present in synaptosomal membranes of rat brain related to anxiety disorders, depression and pain was evaluated by displacement of labeled specific ligands: [3 H] FNZ (binding site for benzodiazepines, in the GABAA receptor), [3H] 8-OH-DPAT (serotonin 5-HT1A) and [3H] DAMGO (µ-opioid). One of the most active compound in the binding inhibition of [3H] DAMGO, was 5´-methyl-2´-hydroxy-3´-nitrochalcone, which presented a Ki value of 13.5± 6.9 microM. In acute chemical and thermal models of nociception in mice, it exerted antinociceptive action without showing sedative, anxiolytic, antidepressant and motor incoordination effects. Blockade in vivo assays revealed that mu opioid receptors are involved in its mechanism of action.