Evaluation of thionolactones as a new type of hydrogen sulfide (H2S) donors for a blood pressure regulation

Bioorg Chem. 2021 Mar:108:104650. doi: 10.1016/j.bioorg.2021.104650. Epub 2021 Jan 12.

Abstract

Hydrogen sulfide (H2S) is a gaseous molecule that exhibits various biological effects. For example, H2S has been recognized as a blood pressure-lowering agent. Presented in this report is a new modifiable platform for H2S supply, its preparation and H2S release kinetics from a series of structurally diversified thionolactones. Furthermore, the properties of the obtained H2S donors were evaluated in both in vitro and in vivo studies. The kinetic parameters of H2S release were determined and compared with NaHS and pyrrolidine-2-thione, a thiolactame analog, using a fluorescence detection method based on 7-azido-4-methyl-2H-chromen-2-one probe. We have shown that H2S release rates from the developed compounds are controllable through structural modifications. This study shows that both the thiono-lactone ring's size and the presence of a methyl group in the thiono-lactone ring significantly influenced the rate of H2S release. Finally, we have found a significant hypotensive response to intravenous administration of the developed donors in anesthetized rats.

Keywords: Blood pressure; Cardiovascular; Hydrogen sulfide; Lactones; Thionolactones.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Pressure / drug effects*
  • Dose-Response Relationship, Drug
  • Hydrogen Sulfide / chemistry
  • Hydrogen Sulfide / pharmacology*
  • Injections, Intravenous
  • Kinetics
  • Lactones / administration & dosage
  • Lactones / chemistry
  • Lactones / pharmacology*
  • Male
  • Molecular Structure
  • Rats
  • Rats, Sprague-Dawley
  • Structure-Activity Relationship

Substances

  • Lactones
  • Hydrogen Sulfide