Combining electronic properties and virtual screening for the development of new antioxidants: Trolox‐like compounds as application example

Abstract

Oxidative stress is an imbalance between the production of free radicals and the antioxidant defenses of the organism. Heart diseases, anemia, inflammation, and neurodegenerative disorders have been associated with this biological condition. Trolox is a notable antioxidant drug similar to vitamin E, and it is used to decrease the oxidative stress or repair the damage caused by it. In this work, the virtual screening technique is applied to identify compounds with antioxidant activities similar to Trolox.The antioxidant activity of these compounds was assessments by the mechanisms of hydrogen atom transfer and single electron transfer. Properties such as bond dissociation enthalpy, adiabatic ionization potential, Gibbs free reaction energy, spin density, highest occupied molecular orbital (HOMO), and GAP (HOMO-LUMO) energies, obtained from the DFT approach, point out to the predominance of the HAT mechanism for the antioxidant action of these compounds. The obtained results contribute to a better understanding of the chemical and physical properties responsible for antioxidant activity and the design of new antioxidant agents. K E Y W O R D Santioxidant activity, DFT method, oxidative stress, trolox, virtual screening

Computational Approaches for Cancer-Fighting: From Gene Expression to Functional Foods

“…The screening was performed using the combined score considering bioactive compounds from all libraries: PDB [51], ChEMBL (activity <10 µM) [52], ChEBI [53], kinase inhibitors (ChEMBL) [52], GPCR Ligands (ChEMBL) [52], GPCR ligands (GLASS) [54] and human metabolomic database (HMDB) [55]. Only compounds showing a similarity score >0.6 with the 5 references were considered, since this is suggested to be the lower threshold to expect similar activity based on structure similarity relationships [56]. The resulting bioactive compounds were also analyzed for their pharmacokinetics, drug likeness and medicinal chemistry friendliness using SwissADME [31], to compute the physicochemical descriptors and predict the adsorption, the distribution, the metabolism and the excretion (ADME) parameters of small molecules to support drug discovery [31].…”