title: Design, synthesis and molecular docking of amide and urea derivatives as Escherichia coli PDHc-E1 inhibitors.
abstract: By targeting the ThDP binding site of Escherichia coli PDHc-E1, two new 'open-chain' classes of E. coli PDHc-E1 inhibitors, amide and urea derivatives, were designed, synthesized, and evaluated. The amide derivatives of compound 6d, with 4-NO2 in the benzene ring, showed the most potent inhibition of E. coli PDHc-E1. The urea derivatives displayed more potent inhibitory activity than the corresponding amide derivatives with the same substituent. Molecular docking studies confirmed that the urea derivatives have more potency due to the two hydrogen bonds formed by two NH of urea with Glu522. The docking results also indicate it might help us to design more efficient PDHc-E1 inhibitors that could interact with Glu522.
authors.affiliation: Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry Central China Normal University, Wuhan 430079, China; College of Food Science & Engineering, Wuhan Polytechnic University, Wuhan 430023, China.
authors.forename: Jun-Bo
authors.initials: JB
authors.lastname: He
authors.affiliation: Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry Central China Normal University, Wuhan 430079, China; College of Food Science & Engineering, Wuhan Polytechnic University, Wuhan 430023, China.
authors.forename: Yan-Liang
authors.initials: YL
authors.lastname: Ren
authors.affiliation: Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry Central China Normal University, Wuhan 430079, China; College of Food Science & Engineering, Wuhan Polytechnic University, Wuhan 430023, China.
authors.forename: Qiu-Shuang
authors.initials: QS
authors.lastname: Sun
authors.affiliation: Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry Central China Normal University, Wuhan 430079, China; College of Food Science & Engineering, Wuhan Polytechnic University, Wuhan 430023, China.
authors.forename: Ge-Yun
authors.initials: GY
authors.lastname: You
authors.affiliation: Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry Central China Normal University, Wuhan 430079, China; College of Food Science & Engineering, Wuhan Polytechnic University, Wuhan 430023, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry Central China Normal University, Wuhan 430079, China; College of Food Science & Engineering, Wuhan Polytechnic University, Wuhan 430023, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zou
authors.affiliation: Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry Central China Normal University, Wuhan 430079, China; College of Food Science & Engineering, Wuhan Polytechnic University, Wuhan 430023, China.
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Feng
authors.affiliation: Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry Central China Normal University, Wuhan 430079, China; College of Food Science & Engineering, Wuhan Polytechnic University, Wuhan 430023, China. Electronic address: jianwan@mail.ccnu.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Wan
authors.affiliation: Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry Central China Normal University, Wuhan 430079, China; College of Food Science & Engineering, Wuhan Polytechnic University, Wuhan 430023, China. Electronic address: he1208@mail.ccnu.edu.cn.
authors.forename: Hong-Wu
authors.initials: HW
authors.lastname: He
mesh_terms: D000577:Amides / Q000737:chemistry*; D001665:Binding Sites; D020134:Catalytic Domain; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology; D006860:Hydrogen Bonding; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D030481:Pyruvate Dehydrogenase (Lipoamide) / Q000037:antagonists & inhibitors*; D014508:Urea / Q000737:chemistry*
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D014508:Urea; D030481:Pyruvate Dehydrogenase (Lipoamide)
keywords: Amide and urea derivatives; Molecular docking; PDHc-E1 inhibitors