Synthesis, Biological Evaluation, and Molecular Docking of Ugi Products Containing a Zinc-Chelating Moiety as Novel Inhibitors of Histone Deacetylases

HDAC inhibitors show great promise for the treatment of cancer. As part of a broader effort to explore the SAR of HDAC inhibitors, synthesis, biological evaluation, and molecular docking of novel Ugi products containing a zinc-chelating moiety are presented. One compound shows improved inhibitory potencies compared to SAHA, demonstrating that hindered lipophilic residues grafted on the peptide scaffold of the α-aminoacylamides can be favorable in the interaction with the enzyme.