Non-peptide macrocyclic histone deacetylase inhibitors derived from tricyclic ketolide skeleton.

ABSTRACT: Inhibition of histone deacetylase (HDAC) function is a validated therapeutic strategy for cancer treatment. Of the several structurally distinct small molecule histone deacetylase inhibitors (HDACi) reported, macrocyclic depsipeptides possess the most complex cap groups and have demonstrated excellent HDAC inhibition potency and isoform selectivity. Unfortunately, the development of macrocyclic depsipeptides has been hampered in part because of development problems characteristic of large peptides and the complex reaction schemes required for their synthesis. Herein we report that tricyclic ketolide TE-802 is an excellent mimetic for the peptide backbone of macrocyclic HDACi. Compounds derived from this template are particularly selective against HDACs 1 and 2 with nanomolar inhibitory act

SUBMITTER: Mwakwari SC 

PROVIDER: S-EPMC2924451 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature