Data-Driven Identification of Hydrogen Sulfide Scavengers

Angew Chem Int Ed Engl. 2019 Aug 5;58(32):10898-10902. doi: 10.1002/anie.201905580. Epub 2019 Jul 11.

Abstract

Hydrogen sulfide (H2 S) is an important signaling molecule whose up- and down-regulation have specific biological consequences. Although significant advances in H2 S up-regulation, by the development of H2 S donors, have been achieved in recent years, precise H2 S down-regulation is still challenging. The lack of potent/specific inhibitors for H2 S-producing enzymes contributes to this problem. We expect the development of H2 S scavengers is an alternative approach to address this problem. Since chemical sensors and scavengers of H2 S share the same criteria, we constructed a H2 S sensor database, which summarizes key parameters of reported sensors. Data-driven analysis led to the selection of 30 potential compounds. Further evaluation of these compounds identified a group of promising scavengers, based on the sulfonyl azide template. The efficiency of these scavengers in in vitro and in vivo experiments was demonstrated.

Keywords: H2S; chemical probe; scavenger; sensor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Free Radical Scavengers / chemistry*
  • Free Radical Scavengers / pharmacology
  • HeLa Cells
  • Humans
  • Hydrogen Sulfide / analysis*
  • Hydrogen Sulfide / antagonists & inhibitors
  • Hydrogen Sulfide / pharmacology
  • Methylene Blue / chemistry
  • Mice
  • Molecular Structure
  • Structure-Activity Relationship
  • Survival Analysis

Substances

  • Free Radical Scavengers
  • Methylene Blue
  • Hydrogen Sulfide