Inhibition of PGSH-1 (COX-1) by flavonoids isolated from a neotropical Lauraceae: A docking study
Currently NSAIDs such as ibuprofen, naproxen, and celecoxib are clinical available for pain and inflammation treatment. However, NSAIDs have side effects including gastrointestinal irritation and renal damage, therefore development of new drugs for inhibiting COX-1 and COX-2 are still increasing. On this context, the in vitro ability of 12 flavonoids (five dihydrochalcone, two chalcone, three flavanone, one flavonol and one flavanonol) isolated from Nectandra amazonum for COX-1 inhibition was tested, which was found to be dose dependent. As part of the search of a structure-activity relationship, Autodock Vina was used to dock the compound structures with the active site of the COX-1(PDB: 3N8V). In vitro results showed that chalcone and dihydrochalcone compounds exhibited strong inhibitory properties (IC50: 1.22µM-1.56µM), with reasonable correlations between docking and in vitro results. Some compounds do not correlate with the best poses obtained by Vina. It was considered either the possibility of presence of allosteric sites involved in observed in vitro results or other molecular mechanism not discovered yet. A brief discussion will be presented.