title: Synthesis, antibacterial activity, and biological evaluation of formyl hydroxyamino derivatives as novel potent peptide deformylase inhibitors against drug-resistant bacteria.
abstract: Peptide deformylase (PDF) has been identified as a promising target for novel antibacterial agents. In this study, a series of novel formyl hydroxyamino derivatives were designed and synthesized as PDF inhibitors and their antibacterial activities were evaluated. Among the potent PDF inhibitors (1o, 1q, 1o', 1q', and 1x), in vivo studies showed that compound 1q possesses mild toxicity, a good pharmacokinetic profile and protective effects. The good in vivo efficacy and low toxicity suggest that this class of compounds has potential for development and use in future antibacterial drugs.
authors.affiliation: Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, Department of Chemistry, East China Normal University, Shanghai 200062, China.
authors.forename: Shouning
authors.initials: S
authors.lastname: Yang
authors.affiliation: Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, Department of Chemistry, East China Normal University, Shanghai 200062, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.affiliation: Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, Department of Chemistry, East China Normal University, Shanghai 200062, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Xing
authors.affiliation: Key Laboratory of Brain Functional Genomics, Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, East China Normal University, Shanghai 200062, China. Electronic address: zzhao@brain.ecnu.edu.cn.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, Department of Chemistry, East China Normal University, Shanghai 200062, China.
authors.forename: Fengping
authors.initials: F
authors.lastname: Lv
authors.affiliation: Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, Department of Chemistry, East China Normal University, Shanghai 200062, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: ysyang@mail.shcnc.ac.cn.
authors.forename: Yushe
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, Department of Chemistry, East China Normal University, Shanghai 200062, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: whu@chem.ecnu.edu.cn.
authors.forename: Wenhao
authors.initials: W
authors.lastname: Hu
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D000581:Amidohydrolases; C084507:peptide deformylase
keywords: Drug resistant bacteria; Peptide deformylase inhibitor; Proline derivatives