Discovery of a Potent 9‐Deazaxanthine‐based Agent for the Treatment of Obesity‐Related Non‐alcoholic Fatty Liver Disease. (14th May 2015)

• Record Type: Journal Article
• Authors: Chen, Jinying; Ma, Liang; Huang, Li; Xie, Caifeng; Pei, Heying; He, Linhong; Fu, Suhong; Chen, Lijuan
• Is Part Of: Chemical biology & drug design. Volume 86:Number 1(2015:Jul.)
• Page Start: 846
• Page End: 859
• Publication Date: 2015-05-14
• Subjects: Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.12429
• Languages: English
• ISSNs: 1747-0277

Abstract

<abstract abstract-type="main" id="cbdd12429-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>A series of deazaxanthine‐based derivatives were rationally prepared and evaluated. <bold>8g</bold> exhibited the most potent glucose‐lowering effect on HepG2 cell line and modulated adiponectin and leptin expression in 3T3‐L1 adipocytes. Oral administration of 8g at 25 mg/kg/day for 4 weeks manifested therapeutic effects on high‐fat diet‐induced non‐alcoholic fatty liver disease (NAFLD) by decreasing the weights of the body, liver, and fat. <bold>8g</bold> also modulated the serum levels of fasting glucose and adiponectin, triglycerides, low‐density lipoprotein‐cholesterol, and alanine aminotransferase, as well as the hepatic concentrations of triglycerides, total cholesterol. Moreover, <bold>8g</bold> significantly decreased steatosis and blocked the increase of adipocytes and the size of adipose tissues from NAFLD. In the DIO mice model, <bold>8g</bold> ameliorated the obesity‐related symptoms and normalized serum biomarkers.</p> </abstract>