Thiazolidinedione derivatives as PTP1B inhibitors with antihyperglycemic and antiobesity effects |
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| Authors: | Bharat Raj Bhattarai Bhooshan Kafle Ji-Sun Hwang Deegendra Khadka Sun-Myung Lee Jae-Seung Kang Seung Wook Ham Inn-Oc Han Hwangseo Park Hyeongjin Cho |
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| Institution: | 1. Department of Chemistry, Inha University, Incheon 402-751, Republic of Korea;2. Department of Physiology and Biophysics, College of Medicine, Inha University, Incheon 402-751, Republic of Korea;3. Department of Microbiology, College of Medicine, Inha University, Incheon 402-751, Republic of Korea;4. Department of Chemistry, Chung Ang University, Seoul 156-756, Republic of Korea;5. Department of Bioscience and Biotechnology, Sejong University, Seoul 143-747, Republic of Korea |
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| Abstract: | Benzylidene-2,4-thiazolidinedione derivatives with substitutions on the phenyl ring at the ortho or para positions of the thiazolidinedione (TZD) group were synthesized as PTP1B inhibitors with IC50 values in a low micromolar range. Compound 3e, the lowest, bore an IC50 of 5.0 μM. In vivo efficacy of 3e as an antiobesity and hypoglycemic agent was evaluated in a mouse model system. Significant improvement of glucose tolerance was observed. This compound also significantly suppressed weight gain and significantly improved blood parameters such as TG, total cholesterol and NEFA. Compound 3e was also found to activate peroxisome proliferator-activated receptors (PPARs) indicating multiple mechanisms of action. |
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