Tetrasulfanes as Selective Modulators of the Cellular Thiolstat

Abstract

Naturally occurring polysulfanes often exhibit a wide spectrum of biological activity, which results from their ability to react with, and hence modify cysteine residues in key proteins and enzymes of the cellular thiolstat. Such interactions frequently proceed via S-thiolation of cysteine residues and subsequent formation of Reactive Oxygen Species. Polysulfanes are highly effective, yet also surprisingly selective for cysteine residues and enable the control of numerous cellular processes ranging from an activation of antioxidant defenses to the induction of programed cell death. Unfortunately, the arsenal of natural tri- and tetrasulfanes is limited. Here, we showcase the synthesis of asymmetric tetrasulfanes, which exhibit an interesting nematocidal activity and represent a new generation of tailor-made polysulfanes with potential applications in the field of agriculture and medicine.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus Sulfur and Silicon and the Related Elements.

GRAPHICAL ABSTRACT

Keywords:

• Cysteine
• cellular thiolstat
• nematodes
• polysulfane
• S-thiolation

Acknowledgments

The authors are grateful for financial support from Saarland University, the Government of Saarland (LFFP T/1-14.2.1.1-LFFP 12/23), the Interreg IVa Programme (Corena-Network; 35GR11051), and the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement 215009 RedCat. Ahsan Raza and Sher Ali were in part funded by the DAAD programme for German–Pakistani Research Cooperation (ID-54374219). The authors would further like to thank Dr. Joseph Zapp for the NMR measurements and Thomas Hoffmann for the HRMS measurements.