| Literature DB >> 23252603 |
Linda Marek1, Alexandra Hamacher, Finn K Hansen, Krystina Kuna, Holger Gohlke, Matthias U Kassack, Thomas Kurz.
Abstract
The synthesis and biological evaluation of new potent hydroxamate-based HDAC inhibitors with a novel alkoxyamide connecting unit linker region are described. Biological evaluation includes MTT and cellular HDAC assays on sensitive and chemoresistant cancer cell lines as well as HDAC profiling of selected compounds. Compound 19i (LMK235) (N-((6-(hydroxyamino)-6-oxohexyl)oxy)-3,5-dimethylbenzamide) showed similar effects compared to vorinostat on inhibition of cellular HDACs in a pan-HDAC assay but enhanced cytotoxic effects against the human cancer cell lines A2780, Cal27, Kyse510, and MDA-MB231. Subsequent HDAC profiling yielded a novel HDAC isoform selectivity profile of 19i in comparison to vorinostat or trichostatin A (TSA). 19i shows nanomolar inhibition of HDAC4 and HDAC5, whereas vorinostat and TSA inhibit HDAC4 and HDAC5 in the higher micromolar range.Entities:
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Year: 2013 PMID： 23252603 DOI： 10.1021/jm301254q
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446