2‐Nitrobenzyl Esters of Penam and Cephem Derivatives as Inhibitors of Penicillin‐Binding Proteins
Cédric Brulé, Jérôme Grugier, Alain Brans, Bernard Joris, Eric Sauvage, Georges Dive, Jacqueline Marchand‐Brynaert · Asian Journal of Organic Chemistry · 2013
Abstract 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 microarrays. 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 β‐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.