title: 2-Substituted 4,5-dihydrothiazole-4-carboxylic acids are novel inhibitors of metallo-β-lactamases.
abstract: Bacterial resistance to β-lactam antibiotics caused by class B metallo-β-lactamases (MBL), especially for certain hospital-acquired, Gram-negative pathogens, poses a significant threat to public health. We report several 2-substituted 4,5-dihydrothiazole-4-carboxylic acids to be novel MBL inhibitors. Structure activity relationship (SAR) and molecular modeling studies were performed and implications for further inhibitor design are discussed.
authors.affiliation: Department of Pharmacology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, United States.
authors.forename: Pinhong
authors.initials: P
authors.lastname: Chen
authors.forename: Lori B
authors.initials: LB
authors.lastname: Horton
authors.forename: Rose L
authors.initials: RL
authors.lastname: Mikulski
authors.forename: Lisheng
authors.initials: L
authors.lastname: Deng
authors.forename: Sandeep
authors.initials: S
authors.lastname: Sundriyal
authors.forename: Timothy
authors.initials: T
authors.lastname: Palzkill
authors.forename: Yongcheng
authors.initials: Y
authors.lastname: Song
mesh_terms: D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: C577916:4,5-dihydrothiazole-4-carboxylic acid; D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D013844:Thiazoles; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases