Design, synthesis and biological evaluation of thiazole- and indole-based derivatives for the treatment of type II diabetes.

Abstract

Present studies have shown that the lipid carrier has a significant role in several aspects of metabolic syndrome in A-FABP/ap2-deficient mice, including type 2 diabetes and atherosclerosis. 38 Thiazole- and indole-based derivatives were synthesized and investigated for their inhibitory effects on the production of LPS-stimulated TNF-α. Among them, 12b exhibited an excellent inhibitory efficiency compared to BMS309403 (95% vs. 85%) at the concentration of 10 μM and a binding affinity for ap2 with the apparent K(i) values 33 nM. Oral administration of 12b at a dosage of 50 mg/kg effectively reduced the levels of plasma blood glucose, triglycerides, insulin, total cholesterol and alanine aminotransferase in high-fat/diet-induced obesity model. The results highlighted that 12b was a potent anti-diabetic agent.

• Authors: Qinyuan Xu, Li Huang, Juan Liu, Liang Ma, Tao Chen, Jinying Chen, Fei Peng, Dong Cao, Zhuang Yang, Neng Qiu, Jingxiang Qiu, Guangcheng Wang, Xiaolin Liang, Aihua Peng, Mingli Xiang, Yuquan Wei, Lijuan Chen
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 52 Pg. 70-81 (Jun 2012) ISSN: 1768-3254 [Electronic] France
• PMID: 22483089 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Chemical References

• Blood Glucose
• FABP4 protein, rat
• Fatty Acid-Binding Proteins
• Hypoglycemic Agents
• Indoles
• Insulin
• Lipopolysaccharides
• Thiazoles
• Triglycerides
• Tumor Necrosis Factor-alpha
• Cholesterol
• Alanine Transaminase

Topics

• Administration, Oral
• Alanine Transaminase (metabolism)
• Animals
• Blood Glucose (metabolism)
• Body Weight (drug effects)
• Cell Line
• Cholesterol (blood)
• Diabetes Mellitus, Type 2 (blood, drug therapy, metabolism, physiopathology)
• Drug Design
• Fatty Acid-Binding Proteins (chemistry, metabolism)
• Hypoglycemic Agents (chemical synthesis, chemistry, pharmacology, therapeutic use)
• Indoles (chemical synthesis, chemistry, pharmacology, therapeutic use)
• Insulin (blood)
• Lipopolysaccharides (pharmacology)
• Male
• Mice
• Models, Molecular
• Protein Conformation
• Rats
• Structure-Activity Relationship
• Thiazoles (chemical synthesis, chemistry, pharmacology, therapeutic use)
• Triglycerides (blood)
• Tumor Necrosis Factor-alpha (biosynthesis)