Synthesis and antinociceptive activity of four 1H-isoindolo-1,3(2H)-diones.
Arch Pharm (Weinheim)
; 355(7): e2100423, 2022 Jul.
Article
em En
| MEDLINE
| ID: mdl-35396875
ABSTRACT
The present study aimed to design and synthesize a series of 2-hydroxy-3-(4-aryl-1-piperazinyl)propyl phthalimide derivatives, which are analogs of 1H-pyrrolo[3,4-c]pyridine-1,3(2H)-dione derivatives with proven analgesic effect. In accordance with the basic principle proposed by Lipinski's rule, the probable bioavailabilities of the F1-F4 phthalimides were assessed. The obtained values indicate good absorption after oral administration and the ability to cross the blood-brain barrier. The four compounds F1-F4 differing in the type of pharmacophore in the phenyl group of the 2-hydroxy-3-(4-aryl-1-piperazinyl)propyl on the imide nitrogen atom (R, F1-F3) and the 4-benzhydryl analog (F4) were selected for in vitro and in vivo studies. Based on the in vitro studies, the effects of compounds F1-F4 on cell viability/proliferation and COX-2 levels were evaluated. Moreover, using in vivo methods, the compounds were tested for antinociceptive activity in models of acute pain (the writhing and the hot-plate tests) in mice. Their influence on the motor coordination effect and locomotor activity was also tested. The obtained results revealed that the compounds F1-F4 strongly suppress the pain of peripheral origin and to a lesser extent (F1-F3) pain of central/supraspinal origin. In the in vitro studies, F1-F4 reduced the COX-2 level in lipopolysaccharide-activated RAW 264.7 cells, which suggests their anti-inflammatory activity.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dor
/
Analgésicos
Limite:
Animals
Idioma:
En
Revista:
Arch Pharm (Weinheim)
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Polônia