Medicinal Thiols: Current Status and New Perspectives

Abstract

The thiol (-SH) functional group is found in a number of drug compounds and confers a unique combination of useful properties. Thiol-containing drugs can reduce radicals and other toxic electrophiles, restore cellular thiol pools, and form stable complexes with heavy metals such as lead, arsenic, and copper. Thus, thiols can treat a variety of conditions by serving as radical scavengers, GSH prodrugs, or metal chelators. Many of the compounds discussed here have been in use for decades, yet continued exploration of their properties has yielded new understanding in recent years, which can be used to optimize their clinical application and provide insights into the development of new treatments. The purpose of this narrative review is to highlight the biochemistry of currently used thiol drugs within the context of developments reported in the last five years. More specifically, this review focuses on thiol drugs that represent the standard of care for their associated conditions, including N-acetylcysteine, 2,3-meso-dimercaptosuccinic acid, British anti-Lewisite, D-penicillamine, amifostine, and others. Reports of novel dosing regimens, delivery strategies, and clinical applications for these compounds were examined with an eye toward emerging approaches to address a wide range of medical conditions in the future.

N-Acetylcysteine (NAC): Impacts on Human Health

“…NAC is a thiol that acts as an acetylated precursor to the amino acid l -cysteine; it can reduce various radicals, by donating one electron, or acts as a nucleophile by donating one or two electrons ( Figure 1 ) [ 33 , 34 ]. Its chemical structure, formed by the sulfhydryl functional group (–SH) plus an acetyl group (–COCH 3 ) linked to the amino group (NH 2 ), is responsible for its metabolic activities related to the direct and indirect antioxidant action and mucolytic action [ 35 ].…”

Mechanics Insights of Alpha-Lipoic Acid against Cardiovascular Diseases during COVID-19 Infection

“…Acetaminophen (paracetamol) is one of the most widely used and well-tolerated analgesic antipyretic drugs, but at overdoses, it can induce hepatic necrosis via its highly reactive intermediate metabolite, N-acetyl-para-benzoquinone imine (NAPQI). More specifically, in acetaminophen overdose or when glutathione is depleted by 70%, the excessive amount of NAPQI covalently binds to the hepatic intracellular protein sulfhydryl groups, including those from cytoplasmic or mitochondrial enzymes, and induces hepatic OS, cellular toxicity, and hepatocytolysis, which lead to irreversible hepatic necrosis [ 122 , 123 ]. In these situations, the administration of NAC is authorized, but there are also some experimental studies that highlight the hepatic benefits of ALA both by reducing local OS and by restoring the optimal level of GSH [ 124 , 125 ].…”

Arsenic intoxication: general aspects and chelating agents

“…One of the mechanisms involved in the pathogenesis of As-mediated toxicity is associated with its high affinity to thiol groups in molecules, Cysteine-rich motifs on proteins, and enzymes such as metallochaperones and zinc fingers (Pfaff et al 2019;Shen et al 2013;Shi et al 2004). Monomethylarsenite strongly inhibits pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase (KGDH) complex, whereas inorganic arsenite exerts a more significant effect to PDH.…”