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Molecular docking and binding study of harpagoside and harpagide as novel anti-inflammatory and antianalgesic compound from Harpagophytum procumbens based on their interactions with COX-2 enzyme
Authors: Arian Rahimi, Kasra Razmkhah, Mahboubeh Mehrnia, Arman Mohamadnia, Hassan Sahebjamee, Soheil Salehi, Elham Akbari Asl, Hossein Tahmasebi, Seyed Ataollah Sadat Shandiz, Foad Davouodbeglou, Sara Ghasemi, Noeman Ardalan, Zahra Ghanbari Kordkandi
Number of views: 336
Objective: To clarify the molecular inhibition mechanism of harpagoside and harpagide with
cyclooxygenase-2 (COX-2) as natural potent anti-inflammatory and anti-analgestic compounds
derived from the Harpagophytum species and evaluate the drug-likeness and pharmacokinetic
characteristics of both compounds.
Methods: The X-ray crystal structure of the COX-2 enzyme and harpagoside and harpagide were
retrieved and energetically minimized by SPDV viewer and ChemAxon softwares, respectively.
Then, all nonpolar hydrogens were merged, and partial atomic charges were assigned using the
Gasteiger-Marsili method. The binding sites and surfaces of enzymes were detected. In addition,
docking studies were performed by AutoDock 4.2 using the Lamarckian genetic algorithm. Finally,
the drug-likeness and molecular pharmacokinetic properties of the compounds were calculated.
Results: Molecular docking showed that both harpagoside and harpagide interact with COX-2, and
their binding energies were –9.13 and –5.53 kcal/mol, respectively. Furthermore, interactions were
stabilized for harpagoside and harpagide within the active site of COX-2 by 7 and 10 hydrogen
bonds, respectively. These results suggested that harpagoside and harpagide complied with most
of Lipinski's rules. Bioactivity scores revealed that harpagoside was a moderate G protein-coupled
receptor ligand, nuclear receptor ligand, protease inhibitor and enzyme inhibitor. Harpagide is a
suitable enzyme inhibitor and moderate G protein-coupled receptor ligand, ion channel modulator,
nuclear receptor ligand, and protease inhibitor.
Conclusions: Results clearly revealed that harpagoside and harpagide act as potential highly
selective COX-2 inhibitors. They are safe anti-inflammatory/analgesic compounds compared
with classical non-steroidal anti-inflammatory drugs and could be considered as promising
inflammatory inhibitors of a natural origin.