Etude théorique des métabolites secondaires des végétaux et des composés de synthèse sur le plan de l'activité biologique

Abstract

The modeling of the biomolecular interactions is a powerful technique in dataprocessing simulations. Many models and software allow the simulation of the protein-ligand interactions. Generally the ligand is of small size. Several software of docking was tested on various molecules of synthesis derived from the 1,3 diphényl propyne-2-one and natural polyphenols of the class of the flavonoïds. The evaluation of their energy of interaction with the 15-lipoxygenase and the cyclooxygenase-2, enzymes strongly implied in various metabolic disorders (inflammatory, atherosclerosis, cancerous) made it possible to release those presenting the best inhibiting effect in agreement with the values of the IC 50 obtained from the literature. It is the luteolin and compound l in the case of the 15-lipoxygenase and the compound j in the case of the cyclooxygénase-2. The values of their energy of interaction are respectively of -28.70 Kj/mol., -27.50 Kj/mol and of -28.54 Kj/mol. The absence of experimental data on the biological activity of the natural substances with the cyclooxygénase-2 led us to make a simulation of their energy of interaction with this enzyme using three programs: FlexX, Autodock and X-score. It arises that the luteolin, with a lowest binding energy, presents the best inhibiting effect.. We could improve also the binding energy of the DHB, powerful inhibiting of LOX-3, by changing its carboxylic function by the group CH 2 OH (ΔG = - 21.127 Kj/mol). If the hydroxyl group is placed in position 5 of DHB, the binding energy of compound 9 enhances to -16.959 Kj/mol. The biological potentialities of three compounds were checked by their pharmacokinetic properties, the lowest molecular weight and positive values of Log P. However, it is necessary to check these results by an experimental study