title: Design, synthesis and biological evaluation of novel nicotinamide derivatives bearing a substituted pyrazole moiety as potential SDH inhibitors.
abstract: BACKGROUND
  Succinate dehydrogenase (SDH) plays an important role in the Krebs cycle, which is considered as an attractive target for development of succinate dehydrogenase inhibitors (SDHIs) based on antifungal agents. Thus, in order to discover novel molecules with high antifungal activities, SDH as the target for a series of novel nicotinamide derivatives bearing substituted pyrazole moieties were designed and synthesised via a one-pot reaction.
  
  
  RESULTS
  The biological assay data showed that compound 3 l displayed the most potent antifungal activity with EC50values of 33.5 and 21.4 µm against Helminthosporium maydis and Rhizoctonia cerealis, respectively. Moreover, 3 l exhibited the best inhibitory ability against SDH enzymes. The results of docking simulation showed that 3 l was deeply embedded into the SDH binding pocket, and the binding model was stabilised by a cation-π interaction with Arg 43, Tyr 58 and an H-bond with Trp 173.
  
  
  CONCLUSIONS
  The study suggests that the pyrazole nicotinamide derivative 3 l may serve as a potential SDHI that can be used as a novel antifungal agent, and provides valuable clues for the further design and optimisation of SDH inhibitors. © 2016 Society of Chemical Industry.
authors.affiliation: School of Plant Protection, Anhui Agricultural University, Hefei, P.R. China.|School of Science, Anhui Agricultural University, Hefei, P.R. China.
authors.forename: Xian-Hai
authors.initials: XH
authors.lastname: Lv
authors.affiliation: School of Plant Protection, Anhui Agricultural University, Hefei, P.R. China.
authors.forename: Zi-Li
authors.initials: ZL
authors.lastname: Ren
authors.affiliation: School of Plant Protection, Anhui Agricultural University, Hefei, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: School of Plant Protection, Anhui Agricultural University, Hefei, P.R. China.
authors.forename: Bing-Xin
authors.initials: BX
authors.lastname: Li
authors.affiliation: School of Medical Engineering, Hefei University of Technology, Hefei, P.R. China.
authors.forename: Qing-Shan
authors.initials: QS
authors.lastname: Li
authors.affiliation: School of Science, Anhui Agricultural University, Hefei, P.R. China.
authors.forename: Ming-Jie
authors.initials: MJ
authors.lastname: Chu
authors.affiliation: School of Plant Protection, Anhui Agricultural University, Hefei, P.R. China.
authors.forename: Hai-Qun
authors.initials: HQ
authors.lastname: Cao
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D020134:Catalytic Domain; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006375:Helminthosporium / Q000187:drug effects; D062105:Molecular Docking Simulation; D009536:Niacinamide / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D011720:Pyrazoles / Q000737:chemistry*; D012232:Rhizoctonia / Q000187:drug effects; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D011720:Pyrazoles; D009536:Niacinamide; D013385:Succinate Dehydrogenase
keywords: molecule docking; nicotinamide; pyrazole; succinate dehydrogenase inhibitors