Trapoxins histone deacetylase HDAC

Recently, psammaplins were reported as potent histone deacetylase (HDAC) and DNA methyltransferase (DNMT) inhibitors (see Table X) (772). Eleven psammaplins (see Table X), isolated from the sponge Pseudoceratina purpurea, were tested in the histone deacetylase (HDAC) enzyme assay at concentrations ranging from 16 nM to 10 pM, and the data obtained were compared to that of two standards, trichostatin A 300) and trapoxin A 301). There were three psammaplin derivatives whose IC50 values were in a... 

In 1993, Yoshida et al. pubhshed trapoxin (TPX, Fig. 3), a fimgal product, which, in contrast to TSA, is an irreversible inhibitor of mammalian histone deacetylase [38]. When the epoxide moiety is reduced to the corresponding primary alcohol, HDAC inhibiting activity is completely lost. This observation emphasizes the importance of the oxirane ring, which most likely binds irreversibly via ring opening at the activated 2-position to a nucleophihc active site residue. 

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