Synthesis, activity, and docking study of phenylthiazole acids as potential agonists of PPARγ
Liang Ma,1,* Taijin Wang,2,* Min Shi,1 Haoyu Ye2 1Department of Nephrology, Kidney Research Institute, 2State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center of Biotherapy, West China Hospital, West China Medical School of Sichuan University, Chengdu, People&rsquo...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2016-05-01
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| Series: | Drug Design, Development and Therapy |
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| Online Access: | https://www.dovepress.com/synthesis-activity-and-docking-study-of-phenylthiazole-acids-as-potent-peer-reviewed-article-DDDT |
| _version_ | 1818196286082383872 |
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| author | Ma L Wang T Shi M Ye H |
| author_facet | Ma L Wang T Shi M Ye H |
| author_sort | Ma L |
| collection | DOAJ |
| description | Liang Ma,1,* Taijin Wang,2,* Min Shi,1 Haoyu Ye2 1Department of Nephrology, Kidney Research Institute, 2State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center of Biotherapy, West China Hospital, West China Medical School of Sichuan University, Chengdu, People’s Republic of China *These authors contributed equally to this work Abstract: Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-mediated transcription factor playing key roles in glucose and lipid homeostasis, and PPARγ ligands possess therapeutic potential in these as well as other areas. In this study, a series of phenylthiazole acids have been synthesized and evaluated for agonistic activity by a convenient fluorescence polarization-based PPARγ ligand screening assay. Compound 4t, as a potential PPARγ agonist with half maximal effective concentration (EC50) 0.75±0.20 µM, exhibited in vitro potency comparable with a 0.83±0.14 µM of the positive control rosiglitazone. Molecular docking and molecular dynamics simulations indicated that phenylthiazole acid 4t interacted with the amino acid residues of the active site of the PPARγ complex in a stable manner, consistent with the result of the in vitro ligand assay. Keywords: PPARγ, phenylthiazole acids, ligand screening assay, docking study |
| first_indexed | 2024-12-12T01:31:40Z |
| format | Article |
| id | doaj.art-89905d2a0f364784b17948b301fc6b9e |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-12-12T01:31:40Z |
| publishDate | 2016-05-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-89905d2a0f364784b17948b301fc6b9e2022-12-22T00:42:58ZengDove Medical PressDrug Design, Development and Therapy1177-88812016-05-012016Issue 11807181527204Synthesis, activity, and docking study of phenylthiazole acids as potential agonists of PPARγMa LWang TShi MYe HLiang Ma,1,* Taijin Wang,2,* Min Shi,1 Haoyu Ye2 1Department of Nephrology, Kidney Research Institute, 2State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center of Biotherapy, West China Hospital, West China Medical School of Sichuan University, Chengdu, People’s Republic of China *These authors contributed equally to this work Abstract: Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-mediated transcription factor playing key roles in glucose and lipid homeostasis, and PPARγ ligands possess therapeutic potential in these as well as other areas. In this study, a series of phenylthiazole acids have been synthesized and evaluated for agonistic activity by a convenient fluorescence polarization-based PPARγ ligand screening assay. Compound 4t, as a potential PPARγ agonist with half maximal effective concentration (EC50) 0.75±0.20 µM, exhibited in vitro potency comparable with a 0.83±0.14 µM of the positive control rosiglitazone. Molecular docking and molecular dynamics simulations indicated that phenylthiazole acid 4t interacted with the amino acid residues of the active site of the PPARγ complex in a stable manner, consistent with the result of the in vitro ligand assay. Keywords: PPARγ, phenylthiazole acids, ligand screening assay, docking studyhttps://www.dovepress.com/synthesis-activity-and-docking-study-of-phenylthiazole-acids-as-potent-peer-reviewed-article-DDDTPPARγPhenylthiazole acidsLigand screening assayDocking study |
| spellingShingle | Ma L Wang T Shi M Ye H Synthesis, activity, and docking study of phenylthiazole acids as potential agonists of PPARγ Drug Design, Development and Therapy PPARγ Phenylthiazole acids Ligand screening assay Docking study |
| title | Synthesis, activity, and docking study of phenylthiazole acids as potential agonists of PPARγ |
| title_full | Synthesis, activity, and docking study of phenylthiazole acids as potential agonists of PPARγ |
| title_fullStr | Synthesis, activity, and docking study of phenylthiazole acids as potential agonists of PPARγ |
| title_full_unstemmed | Synthesis, activity, and docking study of phenylthiazole acids as potential agonists of PPARγ |
| title_short | Synthesis, activity, and docking study of phenylthiazole acids as potential agonists of PPARγ |
| title_sort | synthesis activity and docking study of phenylthiazole acids as potential agonists of ppar gamma |
| topic | PPARγ Phenylthiazole acids Ligand screening assay Docking study |
| url | https://www.dovepress.com/synthesis-activity-and-docking-study-of-phenylthiazole-acids-as-potent-peer-reviewed-article-DDDT |
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