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Angew Chem Int Ed Engl. 2016 Mar 24;55(14):4514-8. doi: 10.1002/anie.201511244. Epub 2016 Jan 28.

Esterase-Sensitive Prodrugs with Tunable Release Rates and Direct Generation of Hydrogen Sulfide.

Author information

1
Department of Chemistry, Georgia State University, Atlanta, GA, 30303-3083, USA.
2
Department of Chemistry, Georgia State University, Atlanta, GA, 30303-3083, USA. wang@gsu.edu.

Abstract

Prodrugs that release hydrogen sulfide upon esterase-mediated cleavage of an ester group followed by lactonization are described herein. By modifying the ester group and thus its susceptibility to esterase, and structural features critical to the lactonization rate, H2 S release rates can be tuned. Such prodrugs directly release hydrogen sulfide without the involvement of perthiol species, which are commonly encountered with existing H2 S donors. Additionally, such prodrugs can easily be conjugated to another non-steroidal anti-inflammatory agent, leading to easy synthesis of hybrid prodrugs. As a biological validation of the H2 S prodrugs, the anti-inflammatory effects of one such prodrug were examined by studying its ability to inhibit LPS-induced TNF-α production in RAW 264.7 cells. This type of H2 S prodrugs shows great potential as both research tools and therapeutic agents.

KEYWORDS:

H2S-NSAIDs; anti-inflammatory drugs; enzyme trigger; hydrogen sulfide prodrugs; lactonization

PMID:
26822005
PMCID:
PMC4902284
DOI:
10.1002/anie.201511244
[Indexed for MEDLINE]
Free PMC Article

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