Identification of novel N-acetylcysteine derivatives for the treatment of hepatocellular injury. Issue 12 (10th November 2017)

• Record Type: Journal Article
• Authors: Liu, Shourong; Zhao, Yanmei; He, Ruoyu; Kong, Limin; Xi, Jianjun; Sun, Jingjing; Shao, Yidan; Pan, Xuwang; Zhang, Jiankang; Zhuang, Rangxiao
• Is Part Of: MedChemComm. Volume 8:Issue 12(2017)
• Page Start: 2238
• Page End: 2247
• Publication Date: 2017-11-10
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19
• DOI: 10.1039/c7md00409e
• Languages: English
• ISSNs: 2040-2503

Abstract

Abstract : N -acetylcysteine (NAC) derivatives were synthesized and screened for anti-hepatocellular injury activities against two different cell models in which the derivatives6a and6b displayed most potent with decreasing malondialdehyde (MDA) level. Abstract : 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 and6b ) displayed more potent activities in decreasing malondialdehyde (MDA) levels than the positive control NAC. In further 4-acetamidophenol (APAP)-induced LO2 cell experiment, compounds6a and6b could not only improve the cell viability but also significantly reduce the secretion of MDA. Additionally, compound6a displayed excellent Caco-2 permeability and oral bioavailability in rats. All these experimental results suggested that compounds6a and6b could serve as potential lead molecules for further development of anti-hepatocellular injury drugs.