Esterase-sensitive prodrugs with tunable release rates and direct generation of hydrogen sulfidea

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, H 2 S release rates can be tuned....

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2016-01, Vol.55 (14), p.4514-4518
Main Authors: Zheng, Yueqin, Yu, Bingchen, Ji, Kaili, Pan, Zhixiang, Chittavong, Vayou, Wang, Binghe
Format: Article
Language:English
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Summary: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, H 2 S release rates can be tuned. Such prodrugs directly release hydrogen sulfide without the involvement of perthiol species, which are commonly encountered with existing H 2 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 H 2 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 H 2 S prodrugs shows great potential as both research tools and therapeutic agents.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201511244