Thiol-Activated 1,2,4-Thiadiazolidin-3,5-diones Release Hydrogen Sulfide through a Carbonyl-Sulfide-Dependent Pathway.

Thiol-Activated 1,2,4-Thiadiazolidin-3,5-diones Release Hydrogen Sulfide through a Carbonyl-Sulfide-Dependent Pathway.
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DOI:
10.1021/acs.joc.2c01220
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发表时间:
2022-09-16
影响因子:
3.6
通讯作者:
Pluth, Michael D.
Pluth, Michael D.
中科院分区:
化学2区
文献类型:
--
作者:
Smith, Haley M.;Pluth, Michael D.

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最近的努力已经扩大了释放重要的生物信号分子硫化氢(H2S)的小分子供体的开发。先前关于1,2,4-噻二唑烷-3,5-二酮(TDZN)的工作报道了这些化合物直接释放H2S,尽管效率低。然而,TDZNs在离体主动脉环舒张模型中显示出有希望的H2S介导的舒张功效。在这里,我们表明,TDZNs有效地释放羰基硫(COS),它可以转化为H2S的酶碳酸酐酶(CA),而不是释放H2S直接如先前报道的。
Recent efforts have expanded the development of small molecule donors that release the important biological signaling molecule hydrogen sulfide (H2S). Prior work on 1,2,4-thiadiazolidin-3,5-diones (TDZNs) reported that these compounds release H2S directly, albeit inefficiently. However, TDZNs showed promising efficacy in H2S-mediated relaxation in ex vivo aortic ring relaxation models. Here we show that TDZNs release carbonyl sulfide (COS) efficiently, which can be converted to H2S by the enzyme carbonic anhydrase (CA) rather than releasing H2S directly as previously reported.
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