150558-35-3Relevant academic research and scientific papers
Structure-activity relationship of sulfonyl piperazine LpxH inhibitors analyzed by an LpxE-coupled malachite green assay
Lee, Minhee,Zhao, Jinshi,Kwak, Seung-Hwa,Cho, Jae,Lee, Myungju,Gillespie, Robert A.,Kwon, Do-Yeon,Lee, Hyunji,Park, Hyun-Ju,Wu, Qinglin,Zhou, Pei,Hong, Jiyong
, p. 641 - 651 (2019)
The UDP-2,3-diacylglucosamine pyrophosphatase LpxH in the Raetz pathway of lipid A biosynthesis is an essential enzyme in the vast majority of Gram-negative pathogens and an excellent novel antibiotic target. The 32P-radioautographic thin-layer chromatography assay has been widely used for analysis of LpxH activity, but it is inconvenient for evaluation of a large number of LpxH inhibitors over an extended time period. Here, we report a coupled, nonradioactive LpxH assay that utilizes the recently discovered Aquifex aeolicus lipid A 1-phosphatase LpxE for quantitative removal of the 1-phosphate from lipid X, the product of the LpxH catalysis; the released inorganic phosphate is subsequently quantified by the colorimetric malachite green assay, allowing the monitoring of the LpxH catalysis. Using such a coupled enzymatic assay, we report the biochemical characterization of a series of sulfonyl piperazine LpxH inhibitors. Our analysis establishes a preliminary structure-activity relationship for this class of compounds and reveals a pharmacophore of two aromatic rings, two hydrophobic groups, and one hydrogen-bond acceptor. We expect that our findings will facilitate the development of more effective LpxH inhibitors as potential antibacterial agents.
LPXH TARGETING COMPOUNDS, COMPOSITIONS THEREOF, AND METHODS OF MAKING AND USING THE SAME
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, (2021/04/17)
LpxH targeting compounds, compositions thereof, as well as methods for for making and using the same are disclosed herein. The LpxH target compounds typically have a structure pursuant to Formula (I) and/or a salt thereof, wherein Rb is selecte
