Syntheses, structures and antibiotic activities of LpxC inhibitors based on the diacetylene scaffold.
Compounds inhibiting LpxC in the lipid A biosynthetic pathway are promising leads for novel antibiotics against multidrug-resistant Gram-negative pathogens. We report the syntheses and structural and biochemical characterizations of LpxC inhibitors based on a diphenyl-diacetylene (1,4-diphenyl-1,3-butadiyne) threonyl-hydroxamate scaffold. These studies provide a molecular interpretation for the differential antibiotic activities of compounds with a substituted distal phenyl ring as well as the absolute stereochemical requirement at the C2, but not C3, position of the threonyl group.
Liang, X; Lee, C-J; Chen, X; Chung, HS; Zeng, D; Raetz, CRH; Li, Y; Zhou, P; Toone, EJ
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