Computational and Retrosynthetic Investigation of Isoxazole‐Bearing Chalcones as Antioxidant Activate Compounds

Abstract

AbstractPeroxiredoxin 5 (1HD2) is an antioxidant enzyme that catalyzes the decrease of peroxide, and act as a regulator of Redox signaling. It is a potential target for working on new antioxidants. 3D‐QSAR method was applied to a set of isoxazoles by using the comparative analysis of molecular fields (CoMFA and CoMSIA). Five new drug candidates (Pr1–Pr5) have been proposed. The study of the interactions between the drug candidate and antioxidant receptor 1HD2 was done by molecular docking. The results of the ADME (Absorption, Distribution, Metabolism, and Excretion) showed that these drug candidates are orally bioavailable and have high gastrointestinal absorption and good permeability. Molecular dynamics was used at 100 ns to study the stability of the MA‐1HD2 and Pr5‐1HD2 complexes obtained after molecular docking. Using the retrosynthesis approach, we have proposed a pathway for synthesizing the drug candidates. This study provides useful information on the antioxidant activity of isoxazole‐based compounds.