Low-molecular-weight thiols (LMWTs)

Low-molecular-weight thiols (LMWTs) are a diverse class of small, sulfur-containing molecules, such as glutathione, cysteine, and mycothiol, that are critical for maintaining the intracellular redox environment (Fahey, 2013). In humans, glutathione (GSH) is the predominant LMWT, serving as a major antioxidant and a cofactor for enzymes involved in the detoxification of reactive oxygen species and xenobiotics (Griffith, 1999). In various pathogenic bacteria, unique LMWTs like mycothiol or bacillithiol are essential for survival under host-induced oxidative stress, making their biosynthetic pathways promising targets for antimicrobial development (Newton et al., 2008). Therapeutically, LMWTs are modulated to either bolster antioxidant defenses, as seen with N-acetylcysteine in acetaminophen overdose, or to deplete cellular protections to enhance the efficacy of chemotherapy and radiation in cancer (Hand & Lozinsky, 2014). Because LMWTs are involved in a wide array of physiological processes, including signal transduction and metal chelation, their pharmacological manipulation requires careful calibration to avoid systemic toxicity (PubChem, 2024).

Other names

Small-molecule thiolsBiothiolsNon-protein thiolsNPSH

Drugs modulate LMWT levels by inhibiting biosynthetic enzymes (e.g., glutamate-cysteine ligase), acting as precursors for synthesis (e.g., NAC), or directly conjugating with the thiol group to facilitate excretion or depletion.