Synthesis of a selective HDAC6 inhibitor active in neuroblasts

Article Article scientifique Article Synthesis of a selective HDAC6 inhibitor active in neuroblasts eng 2016 author Zwick Vincent 595034 author Simoes Avello Claudia 630402 author Nurisso Alessandra 727149 author Petit Charlotte 744534 author Dos Santos Passos Carolina 758055 author Randazzo Giuseppe Marco 796064 author Martinet Nadine author Bertrand Philippe author Cuendet Muriel 0000-0002-1523-1907 686755 4955-4959 10.1016/j.bmcl.2016.09.011 27650925 0960-894X In recent years, the role of HDAC6 in neurodegeneration has been partially elucidated, which led some authors to propose HDAC6 inhibitors as a therapeutic strategy to treat neurodegenerative diseases. In an effort to develop a selective HDAC6 inhibitor which can cross the blood brain barrier (BBB), a modified hydroxamate derivative (compound 3) was designed and synthetized. This compound was predicted to have potential for BBB penetration based on in silico and in vitro evaluation of passive permeability. When tested for its HDAC inhibitory activity, the IC50 value of compound 3 towards HDAC6 was in the nM range in both enzymatic and cell-based assays. Compound 3 showed a cell-based selectivity profile close to that of tubastatin A in SH-SY5Y human neuroblastoma cells, and a good BBB permeability profile. Dewey 615 31 Section des sciences pharmaceutiques 17 false Bioorganic & medicinal chemistry letters 26 20 af3e647a-c31f-4fba-8071-e9500628fbca Article (Published version) Restricted Zwick et al Bioorg Med Chem Let 2016_Neuroblasts.pdf 673925 application/pdf restrictedAccess Faculté des sciences / Section des sciences pharmaceutiques

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Synthesis of a selective HDAC6 inhibitor active in neuroblasts	Bioorganic & medicinal chemistry letters			2016	399	0

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