Design and synthesis of N-benzoyl amino acid derivatives as DNA methylation inhibitors
Davide Garella, Sandra Atlante, Emily Borretto, Mattia Cocco, Marta Giorgis, Annalisa Costale, Livio Stevanato, Gianluca Miglio, Chiara Cencioni, Eli Fernández-de Gortari, José L. Medina-Franco, Francesco Spallotta, Carlo Gaetano and Massimo Bertinaria
Version of Record online: 24 JUN 2016 | DOI: 10.1111/cbdd.12794
A series of N-benzoyl amino acid derivatives was synthesized by modulation of three different molecular moieties (A, B, and C). The ability of synthesized compounds to inhibit DNMT-dependent total DNA methylation was evaluated. The most active compound 22 inhibited both DNMT1- and DNMT3A-mediated DNA methylation in a concentration-dependent manner at micromolar concentration. Docking studies suggest putative binding at the substrate site of both DNMT isoforms studied.