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Thiols, also known as sulfhydryls or mercaptans, are organic compounds containing a functional group composed of a sulfur atom and a hydrogen atom (-SH). In biological systems, thiols such as glutathione (GSH) and cysteine are foundational to cellular redox homeostasis, acting as the primary defense against oxidative stress by neutralizing reactive oxygen and nitrogen species [1, 2]. They play a critical role in protein structure and function, where the reversible formation of disulfide bridges between cysteine residues facilitates proper protein folding and regulates the activity of numerous enzymes and transcription factors [3, 4]. While 'Thiols' as a broad category is not a single therapeutic target, specific thiol-containing molecules and pathways are central to pharmacology. For example, N-acetylcysteine is clinically utilized to replenish glutathione levels during acetaminophen overdose or to reduce mucus viscosity in respiratory diseases [5, 6]. Furthermore, the high nucleophilicity of the thiol group is frequently exploited in medicinal chemistry to design covalent inhibitors that target specific cysteine residues on proteins such as kinases or proteases [7]. Sources: [1] PubChem. (n.d.). 'Thiols'. [2] Forman, H. J., et al. (2009). 'Glutathione: Overview of its protective roles, measurement, and biosynthesis.' Molecular Aspects of Medicine. [3] Giles, N. M., et al. (2003). 'The oxidation of thiol groups in proteins and its biological/pathological implications.' IUBMB Life. [4] StatPearls. (2023). 'Biochemistry, Antioxidants.' [5] NIH LiverTox. (2020). 'N-Acetylcysteine.' [6] Sadowska, A. M., et al. (2006). 'Antioxidant and anti-inflammatory efficacy of NAC in the treatment of COPD.' Therapeutic Advances in Respiratory Disease. [7] Singh, J., et al. (2011). 'The resurgence of covalent drugs.' Nature Reviews Drug Discovery.
Thiols act through redox scavenging of reactive oxygen species (ROS), metal chelation, and thiol-disulfide exchange reactions to maintain cellular antioxidant capacity or neutralize electrophilic toxins.
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