Kinetics and Docking Studies of a COX-2 Inhibitor Isolated from Terminalia bellerica Fruits

Author(s): Tamatam Chandramohan Reddy, Polamarasetty Aparoy, Neela Kishore Babu, Kotha Anil Kumar, Suresh Kumar Kalangi, Pallu Reddanna.

Journal Name: Protein & Peptide Letters

Volume 17 , Issue 10 , 2010

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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 IC50 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 nonsteroidal 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.

Keywords: Triphala, COXIBs, cyclooxygenase-2, gallic acid, non-steroidal anti-inflammatory drugs, Terminalia bellerica

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Article Details

VOLUME: 17
ISSUE: 10
Year: 2010
Page: [1251 - 1257]
Pages: 7
DOI: 10.2174/092986610792231537
Price: $58

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