Hydrogen sulfide: Recent development of its dual donors and hybrid drugs

Hydrogen sulfide (H₂ S) is an important gaseous signalling molecule known to be critically involved in regulating cellular redox homeostasis. As the beneficial and therapeutic effects of H₂ S in pathophysiology, such as in cardiovascular and neurodegenerative diseases, have emerged, so too has the drive for the development of H₂ S-releasing compounds (aka donors) and their therapeutic applications. Most reported donor compounds singularly release H₂ S through biocompatible triggers. An emerging area in the field is the development of compounds that can co-deliver H₂ S with other drugs or biologically relevant species, such as reactive oxygen and nitrogen species (ROS and RNS, respectively). These H₂ 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 H₂ S-based dual donors and hybrid drugs along with their design principles and synergistic effects.