Synthetic chalcones with activity for CNS targets related to anxiety, depression, neurodegenerative diseases and pain

NATALIA COLETTIS; JOSEFINA HIGGS; CRISTINA WASOWSKI; CAROLINA MARCUCCI; DAMIJAN KNEZ; STANISLAV GOBEC; MARIEL MARDER

Buenos Aires

Congreso; 2nd FALAN Congress; 2016

SAN-FALAN

Chalcones are one of the major classes of naturally occurring compounds. Chalcones and their derivatives have a huge importance in medicinal chemistry, displaying a wide range of pharmacological activities including anti-inflammatory, antimicrobial, antioxidant, cytotoxic and antitumor actions. The aim of this work was to synthesize, by aldol condensation, a series of chalcone derivatives and evaluate their potential diverse effects on different biochemical targets involved in CNS disorders such as anxiety, depression, neurodegenerative diseases and pain. We assessed the capacity of these compounds to bind distinct receptors by displacement of labelled specific ligands: [3H] FNZ (binding site of benzodiazepines/GABAA), [3H]8-OH-DPAT (serotonin 5-HT1A) and [3H] DAMGO (μ-opioid). We also studied the inhibition over Aβ aggregation and different enzymes (Monoamine oxidase A&B, acetyl and butyrilcolinesterase). Next, those compounds that showed greater biochemical activities were tested in animal models related to its in vitro effect. In vivo results showed that 5?-methyl-2?-hydroxchalcone exerted anxiolytic effects in the plus maze test. While chalcone nuclei revealed simil-antidepressant activity in the tail suspension test. Also, 5?-methyl-2?-hydroxy-3?-nitrochalcone exhibited antinociceptive action in acute chemical and thermal nociception tests (writhing and hot plate). In conclusion, chalcones are promising compounds for the development of novel drugs with CNS actions.