Synthesis and Evaluation of Antioxidant Activity of Some Novel Hydroxypyridinone Derivatives: A Dft Approach for Explanation of Their Radical Scavenging Activity Publisher



Fassihi A^{1, 2} ; Hasanzadeh F^{1, 2} ; Attar A³ ; Saghaie L^{1, 2} ; Mohammadpour M¹ Show Affiliations
Source: Research in Pharmaceutical Sciences Published:2020

Abstract

Background and purpose: Reactive oxygen species (ROSs) are continuously produced as byproducts of cell metabolism. Free radicals are an unstable form of ROSs with the tendency to react readily with biomolecules such as amino acids, lipids and DNA. These reactions lead to oxidative damages to the cell. Oxidative stress occurs when the concentration of the ROSs exceeds the capacity of antioxidative protection systems of the body. 5-Hydroxypyridin-4-one derivatives can chelate Fe2+and Fe3+due to their α-hydroxyketone moiety. Also, tautomerism in hydroxypyridinone ring leads to enough level of aromaticity resulting in a catechol-like behavior that provides them with good chelating and radical scavenging properties. Experimental approach: Different compounds were synthesized with 5-hydroxypyridine-4-one moiety as the core. The antioxidant properties of molecules were evaluated experimentally by DPPH scavenging method and theoretically using DFT/B3LYP with a 6-31++G (d,p) basis set. Electronic properties were investigated using frontier molecular orbital theory calculations. Furthermore, global descriptive parameters were obtained to find the chemical reactivity of molecules. The natural bond orbital analysis was performed to investigate charge distribution and hydrogen bonding. Findings/Results: Structures of the synthesized compounds were confirmed using IR, 1H-NMR, and 13C-NMR spectral analyses. Among all the synthesized compounds, Va and Vb showed the best antioxidant effect experimentally and computationally. Conclusion and implications: Results of this study were valuable in terms of synthesis, in silico, and in vitro antioxidant evaluations and can be useful for future investigations about the design of novel 5-hydroxypyridin-4-one derivatives possessing iron-chelating and radical scavenging abilities. © 2020 Wolters Kluwer Medknow Publications. All rights reserved.