Esterase-Triggered Self-Immolative Thiocarbamates Provide Insights into COS Cytotoxicity.
ACS Chem Biol
; 14(2): 170-175, 2019 02 15.
Article
em En
| MEDLINE
| ID: mdl-30640440
ABSTRACT
Hydrogen sulfide (H2S) is an important gasotransmitter and biomolecule, and many synthetic small-molecule H2S donors have been developed for H2S-related research. One important class of triggerable H2S donors is self-immolative thiocarbamates, which function by releasing carbonyl sulfide (COS), which is rapidly converted to H2S by the ubiquitous enzyme carbonic anhydrase (CA). Prior studies of esterase-triggered thiocarbamate donors reported significant inhibition of mitochondrial bioenergetics and toxicity when compared to direct sulfide donors, suggesting that COS may function differently than H2S. Here, we report a suite of modular esterase-triggered self-immolative COS donors and include the synthesis, H2S release profiles, and cytotoxicity of the developed donors. We demonstrate that the rate of ester hydrolysis correlates directly with the observed cytotoxicity in cell culture, which further supports the hypothesis that COS functions as more than a simple H2S shuttle in certain biological systems.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Óxidos de Enxofre
/
Tiocarbamatos
/
Esterases
Limite:
Humans
Idioma:
En
Revista:
ACS Chem Biol
Ano de publicação:
2019
Tipo de documento:
Article