当前位置：
X-MOL 学术
›
RSC Med. Chem.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Identification of novel N-acetylcysteine derivatives for the treatment of hepatocellular injury
RSC Medicinal Chemistry ( IF 4.1 ) Pub Date : 2017-10-19 00:00:00 , DOI: 10.1039/c7md00409e Shourong Liu 1 , Yanmei Zhao 1 , Ruoyu He 1 , Limin Kong 2 , Jianjun Xi 1 , Jingjing Sun 1 , Yidan Shao 1 , Xuwang Pan 1 , Jiankang Zhang 1 , Rangxiao Zhuang 1
RSC Medicinal Chemistry ( IF 4.1 ) Pub Date : 2017-10-19 00:00:00 , DOI: 10.1039/c7md00409e Shourong Liu 1 , Yanmei Zhao 1 , Ruoyu He 1 , Limin Kong 2 , Jianjun Xi 1 , Jingjing Sun 1 , Yidan Shao 1 , Xuwang Pan 1 , Jiankang Zhang 1 , Rangxiao Zhuang 1
Affiliation
|
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 (H2O2)-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.
中文翻译：
用于治疗肝细胞损伤的新型 N-乙酰半胱氨酸衍生物的鉴定
目前急需疗效更好、副作用更少的新型抗肝细胞损伤药物。在这项研究中，设计、合成了一系列新型N-乙酰半胱氨酸（NAC）衍生物，并对其针对两种不同细胞模型的抗肝细胞损伤活性进行了生物学评估。在针对过氧化氢 (H 2 O 2 ) 诱导的 LO2 肝细胞的生物学评价中，一半的目标化合物在改善模型细胞活力方面表现出中等到有效的活性，并且两种化合物（ 6a和6b ）在降低丙二醛方面表现出更有效的活性(MDA) 水平高于阳性对照 NAC。在进一步的4-乙酰氨基苯酚（APAP）诱导LO2细胞实验中，化合物6a和6b不仅可以提高细胞活力，而且可以显着减少MDA的分泌。此外，化合物6a在大鼠中表现出优异的 Caco-2 渗透性和口服生物利用度。所有这些实验结果表明化合物6a和6b可以作为进一步开发抗肝细胞损伤药物的潜在先导分子。
更新日期：2017-10-19
中文翻译：
用于治疗肝细胞损伤的新型 N-乙酰半胱氨酸衍生物的鉴定
目前急需疗效更好、副作用更少的新型抗肝细胞损伤药物。在这项研究中，设计、合成了一系列新型N-乙酰半胱氨酸（NAC）衍生物，并对其针对两种不同细胞模型的抗肝细胞损伤活性进行了生物学评估。在针对过氧化氢 (H 2 O 2 ) 诱导的 LO2 肝细胞的生物学评价中，一半的目标化合物在改善模型细胞活力方面表现出中等到有效的活性，并且两种化合物（ 6a和6b ）在降低丙二醛方面表现出更有效的活性(MDA) 水平高于阳性对照 NAC。在进一步的4-乙酰氨基苯酚（APAP）诱导LO2细胞实验中，化合物6a和6b不仅可以提高细胞活力，而且可以显着减少MDA的分泌。此外，化合物6a在大鼠中表现出优异的 Caco-2 渗透性和口服生物利用度。所有这些实验结果表明化合物6a和6b可以作为进一步开发抗肝细胞损伤药物的潜在先导分子。
京公网安备 11010802027423号