title: A study of the effects of substituents on the selectivity of the binding of N-arylaminomethylene malonate inhibitors to DHODH.
abstract: A series of mono- and di-substituted N-arylaminomethylene malonates have been used to probe the potential of utilizing additional H-bonding contacts in the ubiquinone binding channel, for selective inhibition between either human or Plasmodium DHODH. Altered 'head' group functionalities have been utilized in order to probe the role of specific functionalities within the inhibitors in terms of enzyme affinity and selectivity.
authors.affiliation: School of Chemistry, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Deborah
authors.initials: D
authors.lastname: Cowen
authors.forename: Paul
authors.initials: P
authors.lastname: Bedingfield
authors.forename: Glenn A
authors.initials: GA
authors.lastname: McConkey
authors.forename: Colin W G
authors.initials: CW
authors.lastname: Fishwick
authors.forename: A Peter
authors.initials: AP
authors.lastname: Johnson
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D003437:Crotonates; D000090722:Dihydroorotate Dehydrogenase; D006801:Humans; D006885:Hydroxybutyrates / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D008314:Malonates / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D009570:Nitriles; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000187:drug effects / Q000502:physiology; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D014052:Toluidines
chemical_list: D000814:Aniline Compounds; D003437:Crotonates; D000090722:Dihydroorotate Dehydrogenase; D006885:Hydroxybutyrates; D008314:Malonates; D009570:Nitriles; D014052:Toluidines; C527525:teriflunomide; C030290:malonic acid; D044925:Oxidoreductases Acting on CH-CH Group Donors