The outer leaflet of the outer membrane of Gram-negative bacteria consists of the lipid A component of lipopolysaccharide (LPS). Lipid A plays a critical role in eliciting the host response to bacterial infection. As lipid A biosynthesis is required for the survival and fitness of most Gram-negative bacteria, essential lipid A biosynthetic enzymes, including LpxH that is found in the vast majority of Gram-negative human pathogens, are attractive targets for the development of novel antibiotics. Here, we describe the chemical synthesis and LpxH inhibition of a series of sulfonyl piperazine derivatives to establish the structure-activity relationship and binding mode of these novel compounds.

Synthesis and biological evaluation of sulfonyl piperazine derivatives for LpxH inhibition

253rd National Meeting (2017)

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