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Identification of novel N -acetylcysteine derivatives for the treatment of hepatocellular injury.
MedChemComm 2017 December 2
New anti-hepatocellular injury drugs with better curative effects and fewer side effects are urgently needed at present. In this study, a series of novel N -acetylcysteine (NAC) derivatives were designed, synthesized and biologically evaluated for their anti-hepatocellular injury activities against two different cell models. In the biological evaluation against hydrogen peroxide (H2 O2 )-induced LO2 hepatocytes, half of the target compounds exhibited moderate to potent activities in improving the model cell viability, and two compounds ( 6a and 6b ) displayed more potent activities in decreasing malondialdehyde (MDA) levels than the positive control NAC. In further 4-acetamidophenol (APAP)-induced LO2 cell experiment, compounds 6a and 6b could not only improve the cell viability but also significantly reduce the secretion of MDA. Additionally, compound 6a displayed excellent Caco-2 permeability and oral bioavailability in rats. All these experimental results suggested that compounds 6a and 6b could serve as potential lead molecules for further development of anti-hepatocellular injury drugs.
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