Document Detail


Antioxidant activity of the anti-inflammatory compound ebselen: a reversible cyclization pathway via selenenic and seleninic acid intermediates.
MedLine Citation:
PMID:  18932179     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A revised mechanism that accounts for the glutathione peroxidase (GPx)-like catalytic activity of the organoselenium compound ebselen is described. It is shown that the reaction of ebselen with H(2)O(2) yields seleninic acid as the only oxidized product. The X-ray crystal structure of the seleninic acid shows that the selenium atom is involved in a noncovalent interaction with the carbonyl oxygen atom. In the presence of excess thiol, the Se--N bond in ebselen is readily cleaved by the thiol to produce the corresponding selenenyl sulfide. The selenenyl sulfide thus produced undergoes a disproportionation in the presence of H(2)O(2) to produce the diselenide, which upon reaction with H(2)O(2), produces a mixture of selenenic and seleninic acids. The addition of thiol to the mixture containing selenenic and seleninic acids leads to the formation of the selenenyl sulfide. When the concentration of the thiol is relatively low in the reaction mixture, the selenenic acid undergoes a rapid cyclization to produce ebselen. The seleninic acid, on the other hand, reacts with the diselenide to produce ebselen as the final product. DFT calculations show that the cyclization of selenenic acids to the corresponding selenenyl amides is more favored than that of sulfenic acids to the corresponding sulfenyl amides. This indicates that the regeneration of ebselen under a variety of conditions protects the selenium moiety from irreversible inactivation, which may be responsible for the biological activities of ebselen.
Authors:
Bani Kanta Sarma; Govindasamy Mugesh
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Chemistry (Weinheim an der Bergstrasse, Germany)     Volume:  14     ISSN:  1521-3765     ISO Abbreviation:  Chemistry     Publication Date:  2008  
Date Detail:
Created Date:  2008-12-02     Completed Date:  2008-12-29     Revised Date:  2009-08-04    
Medline Journal Info:
Nlm Unique ID:  9513783     Medline TA:  Chemistry     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  10603-14     Citation Subset:  IM    
Affiliation:
Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560 012, India.
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MeSH Terms
Descriptor/Qualifier:
Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*,  chemistry
Antioxidants / chemical synthesis*,  chemistry
Azoles / chemical synthesis*,  chemistry
Catalysis
Computer Simulation
Crystallography, X-Ray
Cyclization
Glutathione Peroxidase / chemistry
Models, Chemical
Models, Molecular
Molecular Structure
Organoselenium Compounds / chemical synthesis,  chemistry*
Oxidation-Reduction
Stereoisomerism
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Antioxidants; 0/Azoles; 0/Organoselenium Compounds; 60940-34-3/ebselen; EC 1.11.1.9/Glutathione Peroxidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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