Quinoline-Glycomimetic Conjugates Reducing Lipogenesis and Lipid Accumulation in Hepatocytes
| Autor: | Amit Chakraborty, Subhadeep Palit, Anindyajit Banerjee, Dipendu Patra, Sanghamitra Mukherjee, Partha Chakrabarti, Sanjay Dutta, Saikat Chakrabarti, Sougata Niyogi |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
biology Organic Chemistry mTORC1 Pharmacology medicine.disease Biochemistry 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine chemistry Glycomimetic 030220 oncology & carcinogenesis Galactosamine Lipogenesis Nonalcoholic fatty liver disease medicine biology.protein Molecular Medicine Molecular Biology Adenosine triphosphate Mechanistic target of rapamycin PI3K/AKT/mTOR pathway |
| Zdroj: | ChemBioChem. 19:1720-1726 |
| ISSN: | 1439-4227 |
| DOI: | 10.1002/cbic.201800271 |
| Popis: | Nonalcoholic fatty liver disease (NAFLD), which is characterized by excess accumulation of triglyceride in hepatocytes, is the major cause of chronic liver disease worldwide and no approved drug is available. The mechanistic target of rapamycin (mTOR) complexes has been implicated in promoting lipogenesis and fat accumulation in the liver, and thus, serve as attractive drug targets. The generation of non- or low cytotoxic mTOR inhibitors is required because existing cytotoxic mTOR inhibitors are not useful for NAFLD therapy. New compounds based on the privileged adenosine triphosphate (ATP) site binder quinoline scaffold conjugated to glucose and galactosamine derivatives, which have significantly low cytotoxicity, but strong mTORC1 inhibitory activity at low micromolar concentrations, have been synthesized. These compounds also effectively inhibit the rate of lipogenesis and lipid accumulation in cultured hepatocytes. This is the first report of glycomimetic-quinoline derivatives that reduce lipid load in hepatocytes. |
| Databáze: | OpenAIRE |
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