Lactones and thiolactones

Lactones and thiolactones are cyclic organic compounds characterized by a closed ring containing an ester or thioester linkage, respectively. They do not represent a single biological target like a receptor or enzyme but are instead a broad class of chemical functional groups found in various drugs and endogenous molecules. In pharmacology, the lactone ring is frequently employed as a prodrug moiety, as seen in HMG-CoA reductase inhibitors like lovastatin, which require hydrolysis to their active hydroxy acid form (PubChem). Endogenously, N-acyl homoserine lactones (AHLs) are critical signaling molecules used by Gram-negative bacteria for quorum sensing to coordinate virulence and biofilm formation (Miller & Bassler, 2001). Thiolactones, such as homocysteine thiolactone, are reactive intermediates in amino acid metabolism that can cause protein damage through N-homocysteinylation, contributing to cardiovascular disease (Jakubowski, 2000). Enzymes known as lactonases, including the paraoxonase (PON) family, are responsible for the hydrolysis and detoxification of these cyclic compounds in humans (Draganov et al., 2005). Because of their diverse roles, they are studied both as structural components of therapeutic agents and as indirect targets for quorum-quenching strategies in infectious diseases. Their biological activity is largely defined by the stability of the cyclic ring and the specificity of the enzymes that catalyze their opening.

Other names

Cyclic estersCyclic thioestersN-acyl homoserine lactonesAHLsHomocysteine thiolactone

Lactones and thiolactones typically serve as prodrugs or signaling molecules that are activated or deactivated via enzymatic hydrolysis by lactonases or esterases (e.g., PON1), or they act as ligands for bacterial transcription factors like LuxR in quorum sensing (Miller & Bassler, 2001; Draganov et al., 2005).