Kinetics and docking studies of a COX-2 inhibitor isolated from Terminalia bellerica fruits.
Protein Pept Lett
; 17(10): 1251-7, 2010 Oct.
Article
en En
| MEDLINE
| ID: mdl-20441561
ABSTRACT
Triphala is an Ayurvedic herbal formulation consisting of equal parts of three myrobalans Terminalia chebula, Terminalia bellerica and Emblica officinalis. We recently reported that chebulagic acid (CA) isolated from Terminalia chebula is a potent COX-2/5-LOX dual inhibitor. In this study, compounds isolated from Terminalia bellerica were tested for inhibition against COX and 5-LOX. One of the fractionated compounds showed potent inhibition against COX enzymes with no inhibition against 5-LOX. It was identified as gallic acid (GA) by LC-MS, NMR and IR analyses. We report here the inhibitory effects of GA, with an IC(50) value of 74 nM against COX-2 and 1500 nM for COX-1, showing ≈20 fold preference towards COX-2. Further docking studies revealed that GA binds in the active site of COX-2 at the non-steroidal anti-inflammatory drug (NSAID) binding site. The carboxylate moiety of GA interacts with Arg120 and Glu524. Based on substrate dependent kinetics, GA was found to be a competitive inhibitor of both COX-1 and COX-2, with more affinity towards COX-2. Taken together, our studies indicate that GA is a selective inhibitor of COX-2. Being a small natural product with selective and reversible inhibition of COX-2, GA would form a lead molecule for developing potent anti-inflammatory drug candidates.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Terminalia
/
Inhibidores de la Ciclooxigenasa 2
/
Frutas
/
Ácido Gálico
Límite:
Animals
Idioma:
En
Revista:
Protein Pept Lett
Asunto de la revista:
BIOQUIMICA
Año:
2010
Tipo del documento:
Article
País de afiliación:
India