Synthesis, biological evaluation, and molecular docking of Ugi products containing a zinc-chelating moiety as novel inhibitors of histone deacetylases

  • J Med Chem. 2009 May 14;52(9):2776-85. doi: 10.1021/jm801529c.
Ambra A Grolla  1 ,  Valeria Podestà ,  Maria Giovanna Chini ,  Simone Di Micco ,  Antonella Vallario ,  Armando A Genazzani ,  Pier Luigi Canonico ,  Giuseppe Bifulco ,  Gian Cesare Tron ,  Giovanni Sorba ,  Tracey Pirali
Affiliations
  • 1. Dipartimento di Scienze Chimiche, Alimentari, Farmaceutiche e Farmacologiche and Drug and Food Biotechnology Center, Universita degli Studi del Piemonte Orientale A. Avogadro, Via Bovio 6, 28100 Novara, Italy.
PMID: 19344175 DOI: 10.1021/jm801529c
Abstract

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 alpha-aminoacylamides can be favorable in the interaction with the enzyme.