title: 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.
authors.affiliation: Department of Chemistry, Jilin University, Changchun, PR China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Liang
authors.forename: Chul-Jin
authors.initials: CJ
authors.lastname: Lee
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.forename: Hak Suk
authors.initials: HS
authors.lastname: Chung
authors.forename: Daina
authors.initials: D
authors.lastname: Zeng
authors.forename: Christian R H
authors.initials: CR
authors.lastname: Raetz
authors.forename: Yaoxian
authors.initials: Y
authors.lastname: Li
authors.forename: Pei
authors.initials: P
authors.lastname: Zhou
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Toone
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D029968:Escherichia coli Proteins; D000581:Amidohydrolases; C097307:UDP-3-O-acyl-N-acetylglucosamine deacetylase