کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2512341 | 1118339 | 2013 | 8 صفحه PDF | دانلود رایگان |
Natural product-inspired discovery of new drug leads plays a key role in drug development. Recently, small-molecule JAK inhibitors have been pursued for the development of anticancer therapeutics. However, most of these inhibitors reported up to now are multi-nitrogen polycyclic aromatic heterocycles. Undoubtedly, the discovery of new types of promising JAK-inhibitory leads is pivotal for JAK inhibitor-based anticancer drug development. Herein we report an unprecedented sesquiterpenoid-alkaloid named thespesilactam, containing a benzo[cd]indole scaffold, from the heartwood of the Portia tree, Thespesia populnea. Its 3-O-Me product, i.e. 8-hydroxy-5-isopropyl-3-methoxy-7-methylbenzo[cd]indol-2(1H)-one, named 3-O-methylthespesilactam, of which the structure was identified by NMR investigations and single-crystal X-ray diffraction analysis, was discovered as a new type of small-molecule anticancer pan-JAK inhibitor against A2058 human melanoma cells, and selective and potent inhibitor of JAK1 and TYK2.
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Journal: Biochemical Pharmacology - Volume 86, Issue 10, 15 November 2013, Pages 1411–1418