کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1374086 | 981912 | 2012 | 6 صفحه PDF | دانلود رایگان |
A large set of N5-derivatives of cerpegin (1,1,5-trimethyl furo[3,4-c]pyridine-3,4-dione) was designed and synthesized in high yields by a simple and handy method using various primary amines for a pyridine cycle synthesis. The effects of 29 derivatives on the three types of catalytic sites of purified mammalian 20S proteasomes (CT-L, T-L and PA) were measured. Most of the new compounds specifically inhibited the PA activity, in the micromolar range. Docking experiments support these results. Moreover, neither calpain I nor cathepsin B were inhibited.
A new class of 20S proteasome inhibitors, derived from the 1,1,5-trimethyl furo[3,4-c]pyridine-3,4-dione scaffold of cerpegin, is described. Most of them specifically inhibited the post-acid (PA) activity of mammalian proteasomes. Docking experiments performed on representative members of this new class corroborate the specificities observed in vitro and suggest a model for inhibition.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 22, Issue 11, 1 June 2012, Pages 3822–3827