Research progress of LpxC inhibitor on Gram-negative bacteria

Abstract

UDP-3-O-acyl-N-acetylglucosamine deacetylase (LpxC) is a metalloprotein that utilizes zinc as a cofactor. LpxC plays a crucial role in catalyzing the synthesis of Lipid A, a major component of the outer membrane lipopolysaccharide in Gram-negative (G-) bacteria, and LpxC shares no common amino acid sequence with various mammalian enzyme proteins. LpxC is essential for the survival of Gram-negative bacteria, making it a promising target for the antibacterial drug development. In recent years, numerous LpxC inhibitors have been reported, which can be broadly categorized into hydroxamic acid and non-hydroxamic acid based on their structural characteristics. Although no LpxC inhibitors are currently available on the market, several candidate small molecules are anticipated to enter clinical trials. The current manuscript offers a comprehensive review of the structures, enzyme catalytic mechanisms, and research progress of novel LpxC inhibitors, with the objective of providing insights and directions for future research in the development of LpxC inhibitors as new antibacterial agents.