Novel aryl carboximidamide and 3-aryl-1,2,4-oxadiazole analogues of naproxen as dual selective COX-2/15-LOX inhibitors: Design, synthesis and docking studies.
Bioorg Chem
; 85: 577-584, 2019 04.
Article
em En
| MEDLINE
| ID: mdl-30878890
ABSTRACT
A series of novel naproxen analogues containing 3-aryl-1,2,4-oxadiazoles moiety (4b-g) and their reaction intermediates aryl carboximidamides moiety (3b-g) was synthesized and evaluated in vitro as dual COXs/15-LOX inhibitors. Compounds 3b-g exhibited superior inhibitory activity than celecoxib as COX-2 inhibitors. Compounds 3b-d and 3g were the most potent COX-2 inhibitors with IC50 range of 6.4 - 8.13â¯nM and higher selectivity indexes (3b, SIâ¯=â¯26.19; 3c, SIâ¯=â¯13.73; 3d, SIâ¯=â¯29.27; 3g, SIâ¯=â¯18.00) comparing to celecoxib (IC50â¯=â¯42.60â¯nM, SIâ¯=â¯8.05). Regarding 15-LOX inhibitory activity, compounds belonging to aryl carboximidamide backbone 3b-e and 3g were the most potent with IC50 range of 1.77-4.91â¯nM comparing to meclofenamate sodium (IC50â¯=â¯5.64⯵M). Data revealed that The levels of NO released by aryl carboximidamides 3b-g were more higher than 3-aryl-1,2,4-oxadiazole derivatives 4b-g, which correlated well with their COX-2 inhibitory activities.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oxidiazóis
/
Naproxeno
/
Inibidores de Lipoxigenase
/
Inibidores de Ciclo-Oxigenase 2
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Bioorg Chem
Ano de publicação:
2019
Tipo de documento:
Article