Histone deacetylase inhibitors with enhanced enzymatic inhibition effects and potent in vitro and in vivo antitumor activities.

ABSTRACT: In the present work, a series of small molecules were designed and synthesized based on structural optimization. A significant improvement in the enzyme inhibitory activity of these compounds was discovered. Moreover, the tested compounds have moderate preference for class I HDACs over HDAC6, as demonstrated by enzyme selectivity assays. In vitro antiproliferation assay results show that representative compounds can selectively inhibit the growth of non-solid lymphoma and leukemic cells such as U937, K562, and HL60. In the in vivo antitumor assay, (S)-4-(2-(5-(dimethylamino)naphthalene-1-sulfonamido)-2-phenylacetamido)-N-hydroxybenzamide (D17) showed better performance than SAHA in blocking U937 tumor growth. Western blot analysis revealed that representative molecules can block the functi

SUBMITTER: Zhang L 

PROVIDER: S-EPMC3947464 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature