Abstract
Histone deacetylase inhibitors with zinc binding groups often exhibit drawbacks like non-selectivity or toxic effects. Thus, there are continuous efforts to modify the currently available inhibitors or to discover new derivatives to overcome these problems. One approach is to synthesize new compounds with novel zinc binding groups. The present study describes the utilization of acyl thiourea functionality, known to possess the ability to complex with metals, to be a novel zinc binding group incorporated into the designed histone deacetylase inhibitors. N-adipoyl monoanilide thiourea (4) and N-pimeloyl monoanilide thiourea (5) have been synthesized and characterized successfully. They showed inhibition of growth of human colon adenocarcinoma and mouse hepatoblastoma cells with low cytotoxic effect against normal human breast cells. Their binding mode to the active site of several histone deacetylases has been studied by docking and the results gave a preliminary indication that they could be successful histone deacetylase inhibitors.
Reference53 articles.
1. Erasers of Histone Acetylation: The Histone Deacetylase Enzymes. Cold Spring Harbor Perspectives in Biology;Seto;Cold Spring Harb Perspect Med.,2014
2. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics;Burtis,2012
3. Targeting class I histone deacetylases in cancer therapy
4. The Process and Strategy for Developing Selective Histone Deacetylase 3 Inhibitors
5. Zinc binding groups for histone deacetylase inhibitors
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