基于功能导向的海洋菲定碱衍生物合成及其作为潜在 PTP1B 抑制剂的特异性选择性。
Function-Oriented Synthesis of Marine Phidianidine Derivatives as Potential PTP1B Inhibitors with Specific Selectivity.
机构信息
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, China.
Nano Science and Technology Institute, University of Science and Technology of China, 166 Ren Ai Road, Suzhou 215123, China.
出版信息
Mar Drugs. 2018 Mar 20;16(3):97. doi: 10.3390/md16030097.
Phidianidines A and B are two novel marine indole alkaloids bearing an uncommon 1,2,4-oxadiazole ring and exhibiting various biological activities. Our previous research showed that the synthesized phidianidine analogs had the potential to inhibit the activity of protein tyrosine phosphatase 1B (PTP1B), a validated target for Type II diabetes, which indicates that these analogs are worth further structural modification. Therefore, in this paper, a series of phidianidine derivatives were designed and rapidly synthesized with a function-oriented synthesis (FOS) strategy. Their inhibitory effects on PTP1B and T-cell protein tyrosine phosphatase (TCPTP) were evaluated, and several compounds displayed significant inhibitory potency and specific selectivity over PTP1B. The structure-activity relationship (SAR) and molecular docking analyses are also described.
菲定碱 A 和 B 是两种新型海洋吲哚生物碱，具有不常见的 1,2,4-噁二唑环，并表现出多种生物活性。我们之前的研究表明，合成的菲定碱类似物具有抑制蛋白酪氨酸磷酸酶 1B（PTP1B）活性的潜力，PTP1B 是 II 型糖尿病的一个已验证的靶点，这表明这些类似物值得进一步进行结构修饰。因此，在本文中，我们采用面向功能的合成（FOS）策略设计并快速合成了一系列菲定碱衍生物。评估了它们对 PTP1B 和 T 细胞蛋白酪氨酸磷酸酶（TCPTP）的抑制作用，一些化合物对 PTP1B 表现出显著的抑制活性和特异性选择性。还描述了构效关系（SAR）和分子对接分析。
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