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

Abstract

Peroxiredoxin 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 isoxazolebased compounds.

Computational Investigation of Isoxazole‐Based Molecules as Potential Drug‐Resistant Anti‐Tuberculosis H37Rv.

“…Molecular alignment is an important stage in generating the best models of CoMSIA. [8] For modeling and optimizing the chemicals in the studied set, we utilized the program Sybyl X-2.0. The geometry of the compounds has been optimized using the field of Tripos forces in 1000 iterations.…”

“…For the Surflex study, the compounds selected for docking were optimized using Gaussian 09 software, using the 6-31G(d,p) basis of the three-parameter Becke Lee-Yang-Parr (B3LYP) functional, which is a kind of density functional theory (DFT) method. [34] The total score of the stable position obtained from each ligand is presented in Table 6.…”

“…In this study, the proposed compounds were optimized by DFT [35] using the hybrid functional B3LYP [36] and taking 6-31G (d) as the basis. The Gaussian 09 software [37] was used to perform the calculations, and the GaussView 6.0 [34,38] to visualize and exploit the results. The optimization was performed in the gas phase.…”

“…The CoMSIA models have to be submitted to an external validation defined by a method of Golbraikh-Tropsha and the method of Roy coefficients (equations (3), ( 4), ( 5), ( 6), ( 8), ( 9), (10), and (11)). [8] Golbraikh-Tropsha's method:…”

A computational study of Di-substituted 1,2,3-triazole derivatives as potential drug candidates against Mycobacterium tuberculosis: 3D-QSAR, molecular docking, molecular dynamics, and ADMETox

“…Due to the therapeutic and biological activities of 1,2,3-triazole, they have been used as anti-inflammatory, 5 antibacterial, 6 antimicrobial, 7 antiproliferative, 8 anticancer, 9 and antiviral agents. 10 This work is aimed at investigating the anti-tuberculosis activity of 24 1,2,3-triazole derivatives synthesized by Costa et al 11 in comparison with rifampicin as the reference drug with antituberculosis activity based on the minimum inhibitory concentration (MIC). 12 A three-dimensional quantitative structureactivity relationship (3D-QSAR) method was used to detect the potential interactions between the proposed 1,2,3-triazole molecules and tuberculosis protein receptors.…”