The first synthesis of natural disulfide bruguiesulfurol and biological evaluation of its derivatives as a novel scaffold for PTP1B inhibitors |
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| Authors: | Jing Chen Cheng-Shi Jiang Wen-Quan Ma Li-Xin Gao Jing-Xu Gong Jing-Ya Li Jia Li Yue-Wei Guo |
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| Institution: | 1. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, PR China;2. Biomedical Science Park of Weifang, Weifang National High-Tech Industrial Development Zone, Weifang, Shandong 261205, PR China |
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| Abstract: | Bruguiesulfurol (1), a cyclic 4-hydroxy-dithiosulfonate isolated from mangrove plant Bruguiera gymnorrhiza, was concisely synthesized for the first time in four steps, and a series of its synthetic derivatives were evaluated for in vitro inhibitory effects on PTP1B and related PTPs. Some derivatives were found to have improved pharmacological profile compared with hit 1. Among them, 5a showed the potent selectivity towards PTP1B over other PTPs, including TCPTP, and 7j exhibited the strongest PTP1B inhibitory activity with an IC50 value of 4.54 μM. |
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| Keywords: | Bruguiesulfurol Derivative PTP1B inhibitor Type 2 diabetes Selectivity |
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