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

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

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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.
* 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
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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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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