Hydrogen Sulfide: Recent Development of Its Dual Donors and Hybrid Drugs.

Hydrogen sulfide (H 2 S) is an important gaseous signaling molecule known to be critically involved in regulating cellular redox homeostasis. As the beneficial and therapeutic effects of H 2 S in pathophysiology, such as in cardiovascular and neurodegenerative diseases, have emerged, so too has the drive for the development of H 2 S-releasing compounds (aka donors) and their therapeutic applications. Most reported donor compounds singularly release H 2 S through biocompatible triggers. An emerging area in the field is the development of compounds that can co-deliver H 2 S with other drugs or biologically relevant species, such as reactive oxygen and nitrogen species (ROS and RNS, respectively). These H 2 S-based dual donors and hybrid drugs are expected to offset negative side effects from individual treatments or achieve synergistic effects rendering them more clinically effective. Additionally, considering that molecules exist and interact physiologically, dual donors may more accurately mimic biological systems as compared to single donors and allow for the elucidation of fundamental chemistry and biology. This review focuses on the recent advances in the development of H 2 S-based dual donors and hybrid drugs along with their design principles and synergistic effects.