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Molecules 2014, 19(5), 6163-6183; doi:10.3390/molecules19056163

Synthesis and Biological Evaluation of Novel Urea- and Guanidine-Based Derivatives for the Treatment of Obesity-Related Hepatic Steatosis

State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Keyuan Road 4, Gaopeng Street, Chengdu 610041, China
These authors contributed equally to this work.
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Author to whom correspondence should be addressed.
Received: 3 March 2014 / Revised: 14 April 2014 / Accepted: 15 April 2014 / Published: 15 May 2014
(This article belongs to the Section Medicinal Chemistry)
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Abstract

Leptin, the product of the obese gene, is an adipocyte-secreted protein hormone playing a key role in the progression of obesity and hepatic steatosis. In this study, 28 novel (thio)urea and guanidine-based analogues have been synthesized and N-(1-(4-(3-(2-chloroethyl)ureido)benzyl)piperidin-4-yl)-3-(trifluoromethyl) benzamide (7i) was found to be a potent regulator of leptin expression in 3T3-L1 adipocytes. Treatment with 7i at a dose of 50 mg/kg/day for 35 days reduced the body weight and liver weight of diet-induced obesity mice by 13.5% and 18.4%, respectively, while also improving the serum levels of triglyceride, total cholesterol, leptin, adiponectin, LDL-c, HDL-c. Hematoxylin-eosin (H&E) and Oil Red O staining also confirmed that 7i ameliorated fat deposition in liver tissue and restricted the size of adipocytes in obesity-related fatty liver disease.
Keywords: leptin; hepatic steatosis; urea and guanidine-based; diet-induced obesity leptin; hepatic steatosis; urea and guanidine-based; diet-induced obesity
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This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Liang, X.; Pei, H.; Ma, L.; Ran, Y.; Chen, J.; Wang, G.; Chen, L. Synthesis and Biological Evaluation of Novel Urea- and Guanidine-Based Derivatives for the Treatment of Obesity-Related Hepatic Steatosis. Molecules 2014, 19, 6163-6183.

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