Synthetic organic polysulfanes as H2S donors and anticancer agents

Organic polysulfanes are one of the major classes of organic sulfur compounds (OSCs) with pharmaceutical and medicinal implications for various diseases. The biological impacts of organic polysulfanes, particularly their role as hydrogen sulfide (H2S) donors, have gained significant attention in scientific research over the past two decades. Notably, H2S has been recognized for its multiple bio-potentials, including its ability to inhibit the proliferation of cancer cells. The feasible reaction of the polysulfane unit of organopolysulfanes with nucleophilic biothiols leads to the sustained release of H2S. The released H2S from various organopolysulfanes opens up new therapeutic windows for utilizing them as potent anticancer and chemopreventive agents for treating different organ-specific cancers. Despite these promising therapeutic implications, a comprehensive understanding of the synthesis and capability of various synthetic organopolysulfanes to release H2S, along with the implications of the released H2S for their pharmacological potentials, remain elusive. Therefore, this review aims to fill the gap by exploring the synthesis and H2S donating capacities of various synthetic organopolysulfanes and their pharmacological benefits for cancer treatment. The insights provided here will help correlate synthetic organopolysulfanes as H2S donors with their therapeutic potentials, offering a clearer perspective on their roles in drug development.