57444-70-9Relevant academic research and scientific papers
Design and synthesis of N-benzoyl amino acid derivatives as DNA methylation inhibitors
Garella, Davide,Atlante, Sandra,Borretto, Emily,Cocco, Mattia,Giorgis, Marta,Costale, Annalisa,Stevanato, Livio,Miglio, Gianluca,Cencioni, Chiara,Fernández-de Gortari, Eli,Medina-Franco, José L.,Spallotta, Francesco,Gaetano, Carlo,Bertinaria, Massimo
, p. 664 - 676 (2016/10/25)
The inhibition of human DNA Methyl Transferases (DNMT) is a novel promising approach to address the epigenetic dysregulation of gene expression in different diseases. Inspired by the validated virtual screening hit NSC137546, a series of N-benzoyl amino acid analogues was synthesized and obtained compounds were assessed for their ability to inhibit DNMT-dependent DNA methylation in vitro. The biological screening allowed the definition of a set of preliminary structure–activity relationships and the identification of compounds promising for further development. Among the synthesized compounds, L-glutamic acid derivatives 22, 23, and 24 showed the highest ability to prevent DNA methylation in a total cell lysate. Compound 22 inhibited DNMT1 and DNMT3A activity in a concentration-dependent manner in the micromolar range. In addition, compound 22 proved to be stable in human serum and it was thus selected as a starting point for further biological studies.
