Evaluation of sulfur, selenium and tellurium catalysts with antioxidant potential.
Oxidative stress is implicated, either directly or indirectly, in the pathology of a range of human diseases. As a consequence, the development of efficient antioxidants for medical use has become increasingly important. We have synthesised a range of structurally related organo-sulfur, -selenium and -tellurium agents and demonstrated that a combination of electrochemical methodology, in vitro assays and cell culture tests can be used to rationalise the antioxidant activity of these catalytic agents. Based on its exceptionally low anodic oxidation potential (Epa) and high activity against the representative oxidative stressors tert-butyl hydroperoxide and peroxynitrite, 4,4'-dihydroxydiphenyltelluride is predicted to be a potent antioxidant. This compound exhibits a correspondingly high activity with a remarkably low IC50 value of 20 nM, when tested in PC12 cell culture using a bioassay indicative of the early stages of Alzheimer's disease.
Giles
Gregory I
GI
School of Biological and Chemical Sciences, University of Exeter, Stocker Road, Exeter, UK EX4 4QD.
Fry
Fiona H
FH
Tasker
Karen M
KM
Holme
Andrea L
AL
Peers
Chris
C
Green
Kim N
KN
Klotz
Lars-Oliver
LO
Sies
Helmut
H
Jacob
Claus
C
D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D002384:Catalysis; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008668:Metallothionein / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D030421:Peroxynitrous Acid / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D012643:Selenium / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013455:Sulfur / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D013691:Tellurium / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D015032:Zinc / Q000737:chemistry / Q000378:metabolism
D000975:Antioxidants; D030421:Peroxynitrous Acid; D013455:Sulfur; D008668:Metallothionein; D006861:Hydrogen Peroxide; D012643:Selenium; D015032:Zinc; D013691:Tellurium