Asparagusic Acid – A Unique Approach toward Effective Cellular Uptake of Therapeutics: Application, Biological Targets, and Chemical Properties

• Published in: ChemMedChem 2023-09, Vol.18 (17), p.e202300143-n/a
• Main Authors: Ņikitjuka, Anna, Žalubovskis, Raivis
• Format: Article
• Language: English
• Subjects: 1,2-dithiolane; asparagusic acid; Biological properties; Carboxylic acids; Chemical properties; Cosmetics; lipoic acid; thiol-disulfide interchange; thiol-mediated uptake
• ISSN: 1860-7179; 1860-7187
• DOI: 10.1002/cmdc.202300143

The synthetic approaches towards unique asparagusic acid and its analogues as well as its chemical use, the breadth of its biological properties and their relevant applications have been explored. The significance of the 1,2‐dithiolane ring tension in dithiol‐mediated uptake and its use for the intracellular transport of molecular cargoes is discussed alongside some of the challenges that arise from the fast thiolate‐disulfide interchange. The short overview with the indication of the available literature on natural 1,2‐dithiolanes synthesis and biological activities is also included. The general review structure is based on the time‐line perspective of the application of asparagusic acid moiety as well as its primitive derivatives (4‐amino‐1,2‐dithiolane‐4‐carboxylic acid and 4‐methyl‐1,2‐dithiolane‐4‐carboxilic acid) used in clinics/cosmetics, focusing on the recent research in this area and including international patents applications. Asparagusic acid: Herein we discuss the recent research on 1,2‐dithiolane‐4‐carboxylic acid moiety with enhanced membrane permeability based on thiol‐mediated cellular uptake. The aspect of application in intracellular transport of molecular cargo, anti‐cancer therapy and improvement of oxidative stress resistance as well as details of important synthetic and experimental procedures are reviewed.