title: 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.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Keyuan Road 4, Gaopeng Street, Chengdu 610041, China.
authors.forename: Qinyuan
authors.initials: Q
authors.lastname: Xu
authors.forename: Li
authors.initials: L
authors.lastname: Huang
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.forename: Liang
authors.initials: L
authors.lastname: Ma
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.forename: Jinying
authors.initials: J
authors.lastname: Chen
authors.forename: Fei
authors.initials: F
authors.lastname: Peng
authors.forename: Dong
authors.initials: D
authors.lastname: Cao
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Yang
authors.forename: Neng
authors.initials: N
authors.lastname: Qiu
authors.forename: Jingxiang
authors.initials: J
authors.lastname: Qiu
authors.forename: Guangcheng
authors.initials: G
authors.lastname: Wang
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Liang
authors.forename: Aihua
authors.initials: A
authors.lastname: Peng
authors.forename: Mingli
authors.initials: M
authors.lastname: Xiang
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
authors.forename: Lijuan
authors.initials: L
authors.lastname: Chen
mesh_terms: D000284:Administration, Oral; D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002460:Cell Line; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D015195:Drug Design; D050556:Fatty Acid-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008958:Models, Molecular; D011487:Protein Conformation; D051381:Rats; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D001786:Blood Glucose; C524662:FABP4 protein, rat; D050556:Fatty Acid-Binding Proteins; D007004:Hypoglycemic Agents; D007211:Indoles; D007328:Insulin; D008070:Lipopolysaccharides; D013844:Thiazoles; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D002784:Cholesterol; D000410:Alanine Transaminase