New benzothiophene derivatives as dual COX-1/2 and 5-LOX inhibitors: synthesis, biological evaluation and docking study.
Future Med Chem
; 9(5): 443-468, 2017 04.
Article
en En
| MEDLINE
| ID: mdl-28362117
AIM: Simultaneous inhibition of 5-LOX/COX may enhance anti-inflammatory effects and reduce side effects. Hence, synthesis of novel dual inhibitors of 5-LOX/COX is an important strategy for treatment of inflammation. Results/methodology: The target compounds were designed to hybridize benzothiophene scaffold or its bioisostere benzofuran with various anti-inflammatory pharmacophore hetercycles through different atoms spacers. Compounds 4a, 4c, 4d, 5b, 7a, showed significant in vitro LOX inhibitory activity higher than that of meclofenamate sodium. Compounds 4b, 4e, 4f, 5a exhibited significant in vitro COX-2 inhibition higher than celecoxib and in vitro LOX inhibitory activity twice that of reference. These compounds elicited significant in vivo anti-inflammatory activities higher than celecoxib in formalin-induced paw edema test. Compound 4e exhibited gastrointestinal safety profile as celecoxib. The results were also consistent with the docking studies. CONCLUSION: Compound 4e could be considered as structural lead for the development of a new class of anti-inflammatory agents with better safety profile.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Tiofenos
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Araquidonato 5-Lipooxigenasa
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Antiinflamatorios no Esteroideos
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Inhibidores de la Lipooxigenasa
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Inhibidores de la Ciclooxigenasa
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Simulación del Acoplamiento Molecular
Límite:
Animals
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Humans
Idioma:
En
Revista:
Future Med Chem
Año:
2017
Tipo del documento:
Article
País de afiliación:
Egipto