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Syntheses, structures and antibiotic activities of LpxC inhibitors based on the diacetylene scaffold.

ABSTRACT: 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.

SUBMITTER: Liang X

PROVIDER: S-EPMC3035996 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Syntheses, structures and antibiotic activities of LpxC inhibitors based on the diacetylene scaffold.

Liang Xiaofei X Lee Chul-Jin CJ Chen Xin X Chung Hak Suk HS Zeng Daina D Raetz Christian R H CR Li Yaoxian Y Zhou Pei P Toone Eric J EJ

Bioorganic & medicinal chemistry 20101209 2

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 a ...[more]

PMID: 21194954

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High susceptibility of MDR and XDR Gram-negative pathogens to biphenyl-diacetylene-based difluoromethyl-allo-threonyl-hydroxamate LpxC inhibitors.

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