کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1364048 | 981527 | 2006 | 27 صفحه PDF | دانلود رایگان |
A series of hydroxamic acid derivatives bearing a cyclic amide/imide group as a linker and/or cap structure, prepared during our structural development studies based on thalidomide, showed class-selective potent histone deacetylase (HDAC)-inhibitory activity. Structure–activity relationship studies indicated that the steric character of the substituent introduced at the cyclic amide/imide nitrogen atom, the presence of the amide/imide carbonyl group, the hydroxamic acid structure, the shape of the linking group, and the distance between the zinc-binding hydroxamic acid group and the cap structure are all important for HDAC-inhibitory activity and class selectivity. A representative compound (30w) showed potent p21 promoter activity, comparable with that of trichostatin A (TSA), and its cytostatic activity against cells of the human prostate cell line LNCaP was more potent than that of the well-known HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA).
We report the design, synthesis, and histone deacetylase-inhibitory activity (including class-selectivity) of a series of hydroxamic acids bearing a cyclic amide/imide as a linker/cap structure.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry - Volume 14, Issue 22, 15 November 2006, Pages 7625–7651