The new H2 S-releasing compound ACS94 exerts protective effects through the modulation of thiol homoeostasis

Journal of Enzyme Inhibition and Medicinal Chemistry
Daniela GiustariniAnna Sparatore

Abstract

The synthesis of a new dithiolethione-cysteine ethyl ester hybrid, ACS94, its metabolites, and its effect on GSH levels in rat tissues and on the concentration of circulating H2S is described. ACS94 rapidly enters the cells, where it is metabolised to cysteine and the dithiolethione moiety ACS48. Experiments performed through the oral administration of ACS94 to healthy rats showed that it is capable of increasing the GSH levels in most of the analysed organs and the concentration of circulating H2S. Although the increase in GSH concentration was similar to that obtained by ACS48 and N-acetylcysteine ethyl ester, the H2S increase was long-lasting and more evident with respect to the parent molecules. Moreover, a decrease of homocysteine in several rat organs and in plasma was noted. This effect may represent a potential therapeutic use of ACS94, as hyperhomocysteinaemia is considered a risk factor for cardiovascular diseases. Lastly, ACS94 was more efficient than N-acetylcysteine in protecting the liver and kidneys against acute acetaminophen toxicity.

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Citations

Jan 24, 2019·Journal of Nephrology·Alessandra F PernaDiego Ingrosso
Nov 2, 2019·Bioscience Reports·Xiran LinZhiqi Song
Dec 31, 2019·Oxidative Medicine and Cellular Longevity·Qin Yang, Guo-Wei He

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Methods Mentioned

BETA
blood collection
acetylation

Software Mentioned

NACET

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