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ID: ALA4715745
Journal: Eur J Med Chem
Title: Synthesis and biological evaluation of novel FK228 analogues as potential isoform selective HDAC inhibitors.
Authors: Narita K,Matsuhara K,Itoh J,Akiyama Y,Dan S,Yamori T,Ito A,Yoshida M,Katoh T
Abstract: Novel C4- and C7-modified FK228 analogues were efficiently synthesized in a highly convergent and unified manner. This synthesis features the amide condensation of glycine-d-cysteine-containing segments with d-valine-containing segments for the direct assembly of the corresponding seco-acids, which are key precursors of macrolactones. The HDAC inhibition assay and cell-growth inhibition analysis of the synthesized analogues revealed novel aspects of their structure-activity relationship. This study demonstrated that simple modification at the C4 and C7 side chains in FK228 is effective for improving both HDAC inhibitory activity and isoform selectivity; moreover, potent and highly isoform-selective class I HDAC1 inhibitors were identified.
CiteXplore: 27318982