title: Synthesis and kinetic testing of new inhibitors for a metallo-β-lactamase from Klebsiella pneumonia and Pseudomonas aeruginosa.
abstract: There are currently no clinically useful inhibitors against metallo-β-lactamases (MBLs), enzymes that confer resistance against a broad spectrum of commonly used antibiotics and that are produced by an increasing number of bacterial pathogens. New pyrrole derivatives were synthesized and assayed for their inhibitory effect on the catalytic activity of the IMP-1 MBL from Pseudomonas aeruginosa and Klebsiella pneumoniae. Six compounds tested (3a-3c, 5, 7 and 8) show micromolar inhibition constants (K(i) values range from ∼10 to 30 μM). In silico docking was employed to investigate the binding mode of the strongest inhibitor, 3b, in the active site of IMP-1. Implications for further improvements of binding efficiency and specificity are discussed.
authors: Helwan University, Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Ein Helwan, Helwan, Egypt.
authors: Mosaad S
authors: MS
authors: Mohamed
authors: Waleed M
authors: WM
authors: Hussein
authors: Ross P
authors: RP
authors: McGeary
authors: Peter
authors: P
authors: Vella
authors: Gerhard
authors: G
authors: Schenk
authors: Rania H
authors: RH
authors: Abd El-Hameed
mesh_terms: D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007710:Klebsiella Infections / Q000188:drug therapy; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000201:enzymology*; D011552:Pseudomonas Infections / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000201:enzymology*; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D011758:Pyrroles; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases