IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Flavone derivatives with broad range of therapeutic effects for Alzheimer´s disease
Autor/es:
KAMECKI F,; COLETTIS N, ; MARCUCCI C, ; RADEMACHER M, ; MARDER M.
Lugar:
Villa Carlos Paz, Cordoba
Reunión:
Congreso; XXXIV Reunión Anual SAN 2019; 2019
Institución organizadora:
Sociedad Argentina de Investigacion en Neurociencias
Resumen:
Alzheimer´s disease (AD) is a multifactorial neurodegenerative disorder. Flavonoids are known for their wide range of CNS-related activities. We aim to develop novel multitarget drugs for AD. We screened a library of synthetic flavonoid derivatives combining different substitutions. All of them showed capacity to bind to the benzodiazepine binding site of the GABAA receptor. We tested them for their capacity to inhibit AChE and BChE (enzymes targeted by AD medications) and MAO A & B (enzymes are altered in AD brain). Most of the flavonoid compounds showed a capacity to inhibit MAO B (IC50 values ranging within 2-22 µM) and also 4 of them inhibited BChE (IC50 for values ranging: 58-68 µM -human enzyme-; 9-19 µM -mice plasma enzyme. Then we assessed in vivo the effect of the administration of a compound which combines the most active substitutions (COMB) in mice. In a novel object recognition task, the previous i.p. injection of COMB (10 mg/kg), 15 min before (1 mg/kg) scopolamine i.p injection (pharmacological AD model) (given 20 min prior training session) prevented mice from scopolamine STM impairment and led mice to express an LTM. No significant effect was observed after the i.p. administration of COMB (1-10 mg/kg) neither in the Plus Maze, Hole-Board nor Locomotor activity tests (given 30 min prior each behavioural assay). COMB seems to be a promising compound with broad range of therapeutic effects for AD patients.