Recent Development of Glucosamine‐6‐phosphate Derivatives as Potential Antibacterial Agents

Abstract

AbstractThe glmS riboswitch (glucosamine‐6‐phosphate activated riboswitch) is located at the 5’‐ untranslated region of the glmS mRNA, which carries the gene of glucosamine‐6‐phosphate (GlcN6P) synthetase named amidotransferase. The glmS riboswitch can bind to its natural coenzyme GlcN6P and lead to its own self‐cleavage, causing the decrease in the expression of the glmS RNA and the synthesis of amidotransferase, and finally, reducing the production of GlcN6P. Since GlcN6P is of vital importance in the metabolic pathway of the bacterial cell wall synthesis, the glmS riboswitch gradually becomes a promising target of antibiotic drugs. In this review, an overview of the development of the glmS riboswitch activators as novel and potent antibacterial agents is described, which involves the structure of the glmS riboswitch and its self‐cleavage mechanism, various the glmS riboswitch activators and their structure‐activity relationships. In particular, the analogs of GlcN6P that can induce self‐cleavage of the glmS riboswitch are highlighted. The most promising compound 9 (Carba‐GlcN6P) exhibited not only excellent activity in inducing the self‐cleavage of the glmS riboswitch, but also great efficacy (kobs=0.153 min−1) at 200 μM compared to GlcN6P (kobs=0.177 min−1).