Document Detail

Cytotoxic and proapototic activities of imidoselenocarbamate derivatives are dependent on the release of methylselenol.
MedLine Citation:
PMID:  23043559     Owner:  NLM     Status:  Publisher    
In the search for new molecules with potential antiangiogenic activity, we found that several imidoselenocarbamate derivatives effectively suppressed the expression of vascular endothelial growth factor (VEGF) induced by hypoxia in NCI-H157 tumor cells. Mechanistic studies indicated that these compounds inhibited STAT3 phosphorylation triggered by hypoxia, suggesting that inhibition of STAT3 function may play a role in VEGF inhibition. Moreover, these molecules showed interesting proapoptotic and antiproliferative effects. Both the presence of selenium, but not sulfur, and the nature of the radical substituents were important for activity. Interestingly, under hypoxic conditions several methyl imidoselenocarbamate derivatives released methylselenol, a highly reactive and cytotoxic gas which was responsible for their biological activities. The kinetics of the release of methylselenol by these molecules was highly dependent on the nature of the substituent radicals and correlated with their early proapoptotic activity. Our results support the notion that pharmacological activities reported for methyl imidoselenocarbamate derivatives are dependent on the release of methylselenol. Given the well-known antitumor activities of this compound, imidoselenocarbamate derivatives represent a promising approach to develop new drugs that release methylselenol in a controlled way.
Alicia Zuazo; Daniel Plano; Elena Ansó; Elena Lizarraga; Maria Font; Juan J Martinez-Irujo
Related Documents :
23721079 - Mild and efficient strategy for site-selective aldehyde modification of glycosaminoglyc...
2116789 - Lack of regio- and stereospecificity in oxidation of (+) camphor by streptomyces griseu...
22399969 - An electrochemical sensor based on nanostructured hollandite-type manganese oxide for d...
3624229 - Structure-mechanism relationships in hemoproteins. oxygenations catalyzed by chloropero...
22936469 - Rhodium-catalyzed direct ch amination of benzamides with aryl azides: a synthetic ro...
11076519 - Electrogenic reactions of cytochrome bd.
15941269 - Catalytic asymmetric vinylation and dienylation of ketones.
8564519 - Zonal differences in nitric oxide synthesis by bovine chondrocytes exposed to interleuk...
6180129 - Changes in the circadian rhythmicity of hydroxyindole-o-methyl transferase (hiomt) acti...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-8
Journal Detail:
Title:  Chemical research in toxicology     Volume:  -     ISSN:  1520-5010     ISO Abbreviation:  Chem. Res. Toxicol.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8807448     Medline TA:  Chem Res Toxicol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

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

Previous Document:  Roles of proteolysis in regulation of GPCR function.
Next Document:  Simple and Rapid Melamine Sensing in Milk Products by Using Surface Enhanced Raman Scattering.