Abstract
The multicomponent synthesis of a mini-library of histone deacetylase inhibitors with imidazo[1,2- a]pyridine-based cap groups is presented. The biological evaluation led to the discovery of the hit compound MAIP-032 as a selective HDAC6 inhibitor with promising anticancer activity. The X-ray structure of catalytic domain 2 from Danio rerio HDAC6 complexed with MAIP-032 revealed a monodentate zinc-binding mode.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Histone Deacetylase 6 / antagonists & inhibitors*
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Histone Deacetylase Inhibitors
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Imidazoles
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Molecular Structure
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Pyridines / chemistry*
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Zebrafish
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Zebrafish Proteins / antagonists & inhibitors*
Substances
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Histone Deacetylase Inhibitors
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Imidazoles
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Pyridines
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Zebrafish Proteins
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HDAC6 protein, zebrafish
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Histone Deacetylase 6