Back to Search
Start Over
Radical Scavenging Potential of the Phenothiazine Scaffold: A Computational Analysis.
- Source :
-
ChemMedChem [ChemMedChem] 2021 Dec 14; Vol. 16 (24), pp. 3763-3771. Date of Electronic Publication: 2021 Oct 15. - Publication Year :
- 2021
-
Abstract
- The reactivity of phenothiazine (PS), phenoselenazine (PSE), and phenotellurazine (PTE) with different reactive oxygen species (ROS) has been studied using density functional theory (DFT) in combination with the QM-ORSA (Quantum Mechanics-based Test for Overall Free Radical Scavenging Activity) protocol for an accurate kinetic rate calculation. Four radical scavenging mechanisms have been screened, namely hydrogen atom transfer (HAT), radical adduct formation (RAF), single electron transfer (SET), and the direct oxidation of the chalcogen atom. The chosen ROS are HO <superscript>.</superscript> , HOO <superscript>.</superscript> , and CH <subscript>3</subscript> OO <superscript>.</superscript> . PS, PSE, and PTE exhibit an excellent antioxidant activity in water regardless of the ROS due to their characteristic diffusion-controlled regime processes. For the HO <superscript>.</superscript> radical, the primary active reaction mechanism is, for all antioxidants, RAF. But, for HOO <superscript>.</superscript> and CH <subscript>3</subscript> OO <superscript>.</superscript> , the dominant mechanism strongly depends on the antioxidant: HAT for PS and PSE, and SET for PTE. The scavenging efficiency decreases dramatically in lipid environment and remains only significant (via RAF) for the most reactive radical (HO <superscript>.</superscript> ). Therefore, PS, PSE, and PTE are excellent antioxidant molecules, especially in aqueous, physiological environments where they are active against a broad spectrum of harmful radicals. There is no advantage or significant difference in the scavenging efficiency when changing the chalcogen since the reactivity mainly derives from the amino hydrogen and the aromatic sites.<br /> (© 2021 The Authors. ChemMedChem published by Wiley-VCH GmbH.)
- Subjects :
- Dose-Response Relationship, Drug
Free Radical Scavengers chemical synthesis
Free Radical Scavengers chemistry
Molecular Structure
Phenothiazines chemical synthesis
Phenothiazines chemistry
Structure-Activity Relationship
Density Functional Theory
Free Radical Scavengers pharmacology
Hydrogen Peroxide antagonists & inhibitors
Phenothiazines pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1860-7187
- Volume :
- 16
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- ChemMedChem
- Publication Type :
- Academic Journal
- Accession number :
- 34536069
- Full Text :
- https://doi.org/10.1002/cmdc.202100546