title: [F01WB-1315 A and B, two dihydroorotate dehydrogenase inhibitors from microbial metabolites].
abstract: OBJECTIVE
  Dihydroorotate Dehydrogenase (DHODH) catalyzes the rate-limiting step in pyrimidine biosynthesis, and its inhibitors have been developed as drugs for treatment of immune diseases. We studied new DHODH inhibitors from microbial metabolites.
  
  
  METHODS
  We established a rapid and effective high throughput screening method for screening DHODH inhibitors from microbial metabolites. The active compounds were isolated from the candidate strain by column chromatography and preparative HPLC.
  
  
  RESULTS
  We picked out F01WB-1315 strain as candidate from 4560 fungal strains. We isolated two active compounds F01WB-1315A and B, with IC50 of 0.07 microg/mL and 0.51 microg/mL, respectively. F01WB-1315B could completely inhibit the spleen lymphocytes proliferation stimulated by ConA in vitro, but F01WB-1315A only had 31.62% inhibitory activity. F01WB-1315A, B were identified to be Ascofuranone and Ascochlorin by their physicochemical properties, MS, 13C-NMR and 1H-NMR analysis.
  
  
  CONCLUSIONS
  F01WB-1315A and B are two strong specific DHODH inhibitors and show moderate inhibitory activity against spleen lymphocytes proliferation.
authors.affiliation: College of Life Science, Hebei Normal University, Shijiazhuang 050016, China. qqj@sohu.com
authors.forename: Qiaojuan
authors.initials: Q
authors.lastname: Qi
authors.forename: Xinhua
authors.initials: X
authors.lastname: Lu
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Zheng
authors.forename: Yeying
authors.initials: Y
authors.lastname: Li
authors.forename: Yuling
authors.initials: Y
authors.lastname: Fan
authors.forename: Jingtong
authors.initials: J
authors.lastname: Zhu
authors.forename: Xiao
authors.initials: X
authors.lastname: Ren
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Cui
authors.forename: Ying
authors.initials: Y
authors.lastname: Shi
authors.forename: Shaojing
authors.initials: S
authors.lastname: Li
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Baohua
authors.initials: B
authors.lastname: Zhao
mesh_terms: D000475:Alkenes / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D000090722:Dihydroorotate Dehydrogenase; D004791:Enzyme Inhibitors / Q000378:metabolism* / Q000494:pharmacology*; D005658:Fungi / Q000378:metabolism*; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000037:antagonists & inhibitors*; D010636:Phenols / Q000378:metabolism / Q000494:pharmacology; D012717:Sesquiterpenes / Q000378:metabolism / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000475:Alkenes; D000090722:Dihydroorotate Dehydrogenase; D004791:Enzyme Inhibitors; D010636:Phenols; D012717:Sesquiterpenes; D044925:Oxidoreductases Acting on CH-CH Group Donors; C006640:ascofuranone; C415745:ascochlorin