Étude in silico des interactions de nouveaux inhibiteurs sur la Cyclooxygénase, cible enzymatique impliquée dans les phénomènes d’inflammation

Abstract

Currently, in silico methods are increasingly use in the strategies of discovery of new molecules for therapeutic purposes. During this research, we have relied on the treatment of inflammatory diseases based on the inhibition of cyclooxygenase-2, an important enzyme involved in the production of prostaglandins, substances that play a key role in inflammation.The main objective of our work is to study by means of molecular docking with Surflex-dock program, the binding modes of a series of small chemicals molecules on the COX-2 target and, then to propose new potential inhibitors for this target.The Surflex-dock software is highly efficient, with a good coefficient of linear correlation (r = -0.63) between affinity and biological activity IC50. So we can, use this program without too much risk of errors to generate by computer simulation novel COX-2 inhibitors. Assessing the affinity of inhibitors derived of PDB made it possible to identify those presenting the best inhibitory effect. Its FLP compound who is the docking score is equal to 5.96 M-1. Molecular docking by Surflex-dock of a collection of 297 similar of inhibitor FLP from the chemical library PubChem with 95% similarity, highlights compounds CID72099 and CID448006 as the best COX-2 inhibitors which have affinities equal to 7.59 M-1 for the first and 7.54 M-1 for the second.In order to validate these results, the in silico prediction of drug similarity positively informs about the ADME-Tox properties of the proposed inhibitors.