Síntese e docking molecular de 1,2,4-oxadiazol como potencial agente antioxidante

Abstract

The present work aimed to synthesize and characterize 1,2,4-oxadiazoles 29a-c, and to evaluate their antioxidant capacity using in vitro and computational methods. For this purpose, the synthesis of an important precursor, the arylamide oximes 27a-c, was carried out using the magnetic stirring method, obtaining excellent yields (84.9% - 95.7%). Then, the synthesis of 1,2,4-oxadiazoles 29a-c was described using the solvent-free method, which does not use solvents, bases or salts, obtaining low to moderate yields (30.6% - 56.2%). Furthermore, these heterocyclics were characterized by IR, 1H NMR and melting point. Thus, with the application of the DPPH• and ABTS•+ free radical scavenging test, it was found that the 1,2,4-oxadiazoles presented better results in reducing these radicals in the ABTS•+ method than in DPPH•, with emphasis on compound 29b (EC50 = 4.055 μg.mL-1), which presented promising free radical scavenging capabilities very similar to the standard antioxidant TROLOX (EC50 = 4.1 μg.mol-1), used as a positive control. Regarding the computational procedures, the molecular docking method was used to verify the energetic stability and the types of interaction of the complexes formed with compounds 29a-c and a pro-oxidant enzyme, Xanthine Oxidoreductase (ID PDB: 1N5X), which is involved in the superoxide release process. Therefore, based on the LGA calculations of the AutoDock 4.2.6 program, it was observed that the 1,2,4-oxadiazoles used as ligands formed stable complexes with the target enzyme, highlighting compound 29c (ΔH = –7.69 kcal.mol-1), which generated a complex with more stable energy close to the original inhibitor ligand, Tei-6720 (ΔH = –8.63 kcal.mol-1), indicating these compounds as potential antioxidants.