Mechanism of Antioxidant Activity of Betanin, Betanidin and Respective C15-Epimers via Shape Theory, Molecular Dynamics, Density Functional Theory and Infrared Spectroscopy

Abstract

Betanin and betanidin are compounds with extensive interest; they are effectively free radical scavengers. The present work aims to elucidate the differences between the mechanism of the antioxidant activity of betanin, betanidin, and their respective C15-epimers. Shape Theory establishes comparisons between the molecules’ geometries and determines parallelisms with the descriptors BDE, PA, ETE IP, PDE, and infrared spectra (IR) obtained from the molecule simulations. Furthermore, the molecules were optimized using the B3LYP/6-31+G(d,p) protocol. Finally, the molecular docking technique analyzes the antioxidant activity of the compounds in the complex with the therapeutic target xanthine oxidase (XO), based on a new proposal for the geometrical arrangement of the ligand atoms in the framework of Shape Theory. The results obtained indicate that the SPLET mechanism is the most favorable in all the molecules studied and that the first group that loses the hydrogen atom in the four molecules is the C17COOH, presenting less PA the isobetanidin. Furthermore, regarding the molecular docking, the interactions of these compounds with the target were favorable, standing out to a greater extent the interactions of isobetanidin with XO, which were analyzed after applying molecular dynamics.

Shape Theory Applied to Molecular Docking and Automatic Localization of Ligand Binding Pockets in Large Proteins

“…In a previous work, 2 we used the enzyme xanthine oxidase (XO), which is distributed in various species, from bacteria to humans, and is present in mammalian tissues. XO contains the cofactor FAD (flavin adenine dinucleotide), a molybdenum cofactor, and [2Fe–2S] centers.…”

“…There is currently a growing interest in the search for therapeutic targets and the development of different computational techniques that support research in the field of pure and applied sciences, such as the area of pharmaceutical chemistry. There is also a marked advance in machine learning techniques, where the shape theory has emerged as a powerful tool in this area. − The union between a molecule and a receptor is the starting point for the design of drugs and their subsequent synthesis …”

“…It allows the conformational space exploration without limitations in the number of atoms of the interacting molecules. The incorporation of the shape theory ,, in the context of molecular docking appeared for the first time in a recent work . Multiple applications in chemistry, physics, and engineering have been reported.…”

“…The incorporation of the shape theory 29,31,34 in the context of molecular docking appeared for the first time in a recent work. 2 Multiple applications in chemistry, physics, and engineering In general, the shape theory is a broad branch of statistics. Initially, models based on the normal distribution received wide diffusion, for example, refs 3038, and 39.…”

“…The incorporation of the shape theory 29 , 31 , 34 in the context of molecular docking appeared for the first time in a recent work. 2 Multiple applications in chemistry, physics, and engineering have been reported. For example, ref ( 3 ) applied the shape theory for spectroscopic analysis and ref ( 35 ) studied rocking curves, both in the context of experimental physics; in engineering, ref ( 36 ) implemented a remote sensing analysis of burning satellite products; finally, in the area that concerns us, ref ( 37 ) set the shape theory for the automatic search of large clusters not assisted by experts.…”