title: Design, synthesis and molecular modeling of novel N-acylhydrazone derivatives as pyruvate dehydrogenase complex E1 inhibitors.
abstract: As potential inhibitors of pyruvate dehydrogenase complex E1 (PDHc-E1), a series of 19 1-((4-amino-2-methylpyrimidin-5-yl)methyl)-5-methyl-N'-(substituent)benzylidene-1H-1,2,3-triazole-4-carbohydrazide 4 has been synthesized and tested for their PDHc-E1 inhibitory activity in vitro. Some of these compounds such as 4a, 4g, 4l, 4o, 4p, and 4q were demonstrated to be effective inhibitors by the bioassay of Escherichia coli PDHc-E1. SAR analysis indicated that the PDHc-E1 inhibitory activity could be further enhanced by optimizing the substituted groups in the parent compound. Molecular modeling study with compound 4o as a model was performed to evaluate docking. The results of modeling study suggested a probable inhibition mechanism.
authors.affiliation: Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, Department of Chemistry, Central China Normal University, Wuhan 430079, People's Republic of China.
authors.forename: Jun-Bo
authors.initials: JB
authors.lastname: He
authors.affiliation: Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, Department of Chemistry, Central China Normal University, Wuhan 430079, People's Republic of China.
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Feng
authors.affiliation: Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, Department of Chemistry, Central China Normal University, Wuhan 430079, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, Department of Chemistry, Central China Normal University, Wuhan 430079, People's Republic of China.
authors.forename: Rui-Juan
authors.initials: RJ
authors.lastname: Tao
authors.affiliation: Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, Department of Chemistry, Central China Normal University, Wuhan 430079, People's Republic of China.
authors.forename: Yan-Liang
authors.initials: YL
authors.lastname: Ren
authors.affiliation: Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, Department of Chemistry, Central China Normal University, Wuhan 430079, People's Republic of 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, Ministry of Education, Department of Chemistry, Central China Normal University, Wuhan 430079, People's Republic of China. Electronic address: he1208@mail.ccnu.edu.cn.
authors.forename: Hong-Wu
authors.initials: HW
authors.lastname: He
mesh_terms: D006835:Hydrazones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D030481:Pyruvate Dehydrogenase (Lipoamide) / Q000037:antagonists & inhibitors*; D011768:Pyruvate Dehydrogenase Complex / Q000037:antagonists & inhibitors* / Q000494:pharmacology
chemical_list: D006835:Hydrazones; D011768:Pyruvate Dehydrogenase Complex; D030481:Pyruvate Dehydrogenase (Lipoamide)
keywords: Molecular modeling; N-Acylhydrazone derivatives; PDHc-E1 inhibitors; Synthesis