1334525-91-5Relevant academic research and scientific papers
Design and synthesis of novel cell wall inhibitors of Mycobacterium tuberculosis GlmM and GlmU
Li, Yongmeng,Zhou, Yan,Mac, Yufang,Li, Xuebing
, p. 1714 - 1720 (2011/12/02)
GlmM and GlmU are key enzymes in the biosynthesis of UDP-N-acetyl-D- glucosamine (UDP-GlcNAc), an essential precursor of peptidoglycan and the rhamnose-GlcNAc linker region in the mycobacterial cell wall. These enzymes are involved in the conversion of two important precursors of UDP-GlcNAc, glucosamine-6-phosphate (GlcN-6-P) and glucosamine-1-phosphate (GlcN-1-P). GlmM converts GlcN-6-P to GlcN-1-P, GlmU is a bifunctional enzyme, whereby GlmU converts GlcN-1-P to GlcNAc-1-P and then catalyzes the formation of UDP-GlcNAc from GlcNAc-1-P and uridine triphosphate. In the present study, methyl 2-amino-2-deoxyl-α-D-glucopyranoside 6-phosphate (1α), methyl 2-amino-2- deoxyl-β-D-glucopyranoside 6-phosphate (1β), two analogs of GlcN-6-P, were synthesized as GlmM inhibitors; 2-azido-2-deoxy-α-D- glucopyranosyl phosphate (2) and 2-amino-2,3-dideoxy-3-fluoro-α- Dglucopyranosyl phosphate (3), analogs of GlcN-1-P, were synthesized firstly as GlmU inhibitors. Compounds 1α, 1β, 2, and 3 as possible inhibitors of mycobacterial GlmM and GlmU are reported herein. Compound 3 showed promising inhibitory activities against GlmU, whereas 1α, 1β and 2 were inactive against GlmM and GlmU even at high concentrations.
