Design,synthesis, and SAR of embelin analogues as the inhibitors of PAI-1 (plasminogen activator inhibitor-1) |
| |
| Institution: | 1. Shanghai Research Center for the Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China;2. State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, PR China;1. Department of Mathematics, Nanjing University, Nanjing, 210093, PR China;2. School of Mathematics and Statistics, Xi’an Jiaotong University, Xi’an, 710049, PR China;3. Department of Mathematics and Statistics, Lanzhou University, Lanzhou, 730000, PR China;1. Laboratório de Farmacognosia, Universidade de Brasília, Campus Universitário Darcy Ribeiro, Asa Norte, CEP 70910-900 Brasília, DF, Brazil;2. Instituto de Química, Universidade Federal do Rio Grande do Norte, Natal, Brazil;3. Laboratório de Anatomia Vegetal, Universidade de Brasília, Brasília, Brazil;4. Departamento de Química Orgânica, Universidade Federal do Ceará, Fortaleza, Brazil;5. Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil;6. FAPERJ/Laboratório de Ciências Químicas/UENF/-Departamento de Química, UFRRJ, Seropédica, Brazil;1. Control System Laboratory, Department of Electrical Engineering, National Cheng Kung University, Tainan 701, Taiwan, ROC;2. Department of Computer Science and Information Engineering, National Cheng Kung University, Tainan 701, Taiwan, ROC;3. Department of Electrical and Computer Engineering, University of Houston, Houston, TX 77204-4005, USA;1. Key Laboratory of Synthetic and Self-Assembly Chemistry for Organic Functional Molecules, Centre for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, 200032, China;2. Wuhan National Laboratory for Optoelectronics, School of Optical and Electronic Information, Huazhong University of Science and Technology, Wuhan, 430074, China |
| |
| Abstract: | The natural product embelin was found to have PAI-1 inhibitory activity with the IC50 value of 4.94 μM. Based on the structure of embelin, a series of analogues were designed, synthesized, and evaluated for their ability to inhibit PAI-1. The SAR study on these compounds disclosed that the inhibitory potency largely depended on the hydroxyl groups at C2 and C5, and the length of the alkyl chains at C3 and C6. Compound 11 displayed the best PAI-1 inhibitory potency with the IC50 value of 0.18 μM. |
| |
| Keywords: | Embelin Natural product PAI-1 Inhibitory activity SAR study |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
