Yamazaki Hiroyuki, Kanno Syu-Ichi, Abdjul Delfly B, Namikoshi Michio
Department of Natural Product Chemistry, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Aoba-ku, Sendai 981-8558, Japan.
Department of Clinical Pharmacotherapeutics, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Aoba-ku, Sendai 981-8558, Japan.
Bioorg Med Chem Lett. 2017 May 15;27(10):2207-2209. doi: 10.1016/j.bmcl.2017.03.033. Epub 2017 Mar 18.
Agelasine G (1), a known bromine-containing diterpene alkaloid, was isolated as a new type of protein tyrosine phosphatase (PTP) 1B inhibitor together with ageline B (2), an inactive debromo-derivative of 1, from the marine sponge Agelas nakamurai collected at Iriomote Island in Okinawa, Japan. Further biological evaluations revealed that compound 1 exhibited selective inhibitory activity against PTP1B over T-cell PTP and CD45 phosphatase. Compound 1 also enhanced the insulin-stimulated phosphorylation levels of Akt in Huh-7 cells more strongly than compound 2. The results obtained in this study suggest that compound 1 activates the insulin signaling pathway by inhibiting PTP1B activity.
从日本冲绳西表岛采集的海洋海绵中分离出已知的含溴二萜生物碱阿吉拉辛G（1），它与阿吉琳B（2）（1的无活性脱溴衍生物）一起作为一种新型蛋白酪氨酸磷酸酶（PTP）1B抑制剂。进一步的生物学评估表明，化合物1对PTP1B的抑制活性比对T细胞PTP和CD45磷酸酶具有选择性。化合物1在Huh-7细胞中比化合物2更强烈地增强了胰岛素刺激的Akt磷酸化水平。本研究获得的结果表明，化合物1通过抑制PTP1B活性激活胰岛素信号通路。
