2‐Nitrobenzyl Esters of Penam and Cephem Derivatives as Inhibitors of Penicillin‐Binding Proteins

Nitroveratrole (NV) esters, that is 4,5-dimethoxy-2-nitrobenzyl esters, of penicillin and cephalosporin derivatives have been prepared in the course of a program that is dedicated to the development of photosensitive protein micro-arrays. Surprisingly, some molecules were revealed to be acylating inhibitors of R39 and BlaR-CTD proteins, which are two representative penicillin-binding proteins, while being bad substrates of beta-lactamases, which are bacterial defense enzymes. Electrostatic potential maps and docking experiments showed that the 2-nitro group of NV esters could play the role of a carboxylate group in the penam series.