Vicinal diaryl azole-based urea derivatives as potential cholesterol lowering agents acting through inhibition of SOAT enzymes
| Autor: | Nirali R. Patel, Niraj N. Mankadia, Hardik Gandhi, Mange Ram Yadav, Prashant R. Murumkar, Mahesh A. Barmade, Satish N. Baldha, Palash Pal, Ashish M. Kanhed |
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| Rok vydání: | 2017 |
| Předmět: |
Azoles
0301 basic medicine 030204 cardiovascular system & hematology Pharmacology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Drug Discovery Animals Humans Urea Enzyme Inhibitors IC50 Triglycerides Hypolipidemic Agents chemistry.chemical_classification Lipoprotein lipase Triglyceride Chemistry Anticholesteremic Agents Organic Chemistry Cholesterol lowering Cholesterol LDL General Medicine Atherosclerosis Lipoprotein Lipase Cholesterol 030104 developmental biology Enzyme Biochemistry Toxicity Azole Vicinal Sterol O-Acyltransferase |
| Zdroj: | European Journal of Medicinal Chemistry. 130:107-123 |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2017.02.038 |
| Popis: | A novel series of vicinal diaryl azole-urea derivatives were synthesized and evaluated for their potential to inhibit SOAT enzyme. Among the reported compounds, compound (12d) emerged as the most potent compound with an IC50 value of 2.43 μM. In polaxamer-407 induced lipoprotein lipase inhibition model, compound (12d) reduced triglyceride turnover in vivo. Compound (12d) also showed dose-dependent prevention of serum total cholesterol and prevention of LDL-C elevation at a dose of 30 mg/kg. Furthermore, compound (12d) showed potential to stop falling levels of serum HDL-C dose-dependently and improved the atherogenic index. Effect of 12d on body weight, plaque formation and development of atherogenic lesions were studied. Toxicological study of compound (12d) indicated that at a dose of 2000 mg/kg, 12d was devoid of any signs of toxicity or mortality. |
| Databáze: | OpenAIRE |
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