title: Potential interaction of natural dietary bioactive compounds with COX-2.
abstract: Bioactive natural products present in the diet play an important role in several biological processes, and many have been involved in the alleviation and control of inflammation-related diseases. These actions have been linked to both gene expression modulation of pro-inflammatory enzymes, such as cyclooxygenase 2 (COX-2), and to an action involving a direct inhibitory binding on this protein. In this study, several food-related compounds with known gene regulatory action on inflammation have been examined in silico as COX-2 ligands, utilizing AutoDock Vina, GOLD and Surflex-Dock (SYBYL) as docking protocols. Curcumin and all-trans retinoic acid presented the maximum absolute AutoDock Vina-derived binding affinities (9.3 kcal/mol), but genistein, apigenin, cyanidin, kaempferol, and docosahexaenoic acid, were close to this value. AutoDock Vina affinities and GOLD scores for several known COX-2 inhibitors significatively correlated with reported median inhibitory concentrations (R² = 0.462, P < 0.001 and R² = 0.238, P = 0.029, respectively), supporting the computational reliability of the predictions made by our docking simulations. Moreover, docking analysis insinuate the synergistic action of curcumin on celecoxib-induced inhibition of COX-2 may occur allosterically, as this natural compound docks to a place different from the inhibitor binding site. These results suggest that the anti-inflammatory properties of some food-derived molecules could be the result of their direct binding capabilities to COX-2, and this process can be modeled using protein-ligand docking methodologies.
authors.affiliation: Environmental and Computational Chemistry Group, University of Cartagena, Cartagena, Colombia.
authors.forename: Wilson
authors.initials: W
authors.lastname: Maldonado-Rojas
authors.forename: Jesus
authors.initials: J
authors.lastname: Olivero-Verbel
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D016718:Arachidonic Acid / Q000737:chemistry; D020134:Catalytic Domain; D000068579:Celecoxib; D003198:Computer Simulation; D003474:Curcumin / Q000737:chemistry; D051546:Cyclooxygenase 2 / Q000737:chemistry*; D052246:Cyclooxygenase 2 Inhibitors / Q000737:chemistry*; D005395:Fish Oils / Q000737:chemistry*; D005502:Food; D057927:Hydrophobic and Hydrophilic Interactions; D014975:Lutein / Q000737:chemistry*; D051379:Mice; D008958:Models, Molecular; D010936:Plant Extracts / Q000737:chemistry*; D011485:Protein Binding; D011720:Pyrazoles / Q000737:chemistry; D013449:Sulfonamides / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D005395:Fish Oils; D010936:Plant Extracts; D011720:Pyrazoles; D013449:Sulfonamides; D016718:Arachidonic Acid; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D003474:Curcumin; D000068579:Celecoxib; D014975:Lutein