Small Molecule Modulators of Sulfur/Selenium Transfer

Abstract

Hydrogen Sulfide (H2S) and its congener Hydrogen Selenide (H2Se) exhibit high toxicity, but are indispensable for maintaining sulfur and selenium homeostasis respectively. Both being a part of the chalcogen family, they share close chemical and biochemical similarities; however, they exhibit significant differences. Our study provides an overview to understand the biochemical variances between these two reactive species by modulating sulfur/selenium transfer within the biological milieu through the development of small molecules. We developed an inhibitor 7 targeting a key enzyme responsible for H2S production, 3-Mercaptopyruvate sulfurtransferase (3-MST). Additionally, we designed a self-immolating selenourea donor 8 equipped with a fluorophore reporter which can be utilised to develop a direct H2Se donor 10. The Prospect of our research extend beyond providing insights into the intricate sulfur and selenium transfer processes in cellulo; it also enables us to modulate their activities.