title: Development of 5-benzylpaullones and paullone-9-carboxylic acid alkyl esters as selective inhibitors of mitochondrial malate dehydrogenase (mMDH).
abstract: A collection of paullones was tested for inhibitory activity against mitochondrial malate dehydrogenase (mMDH) as a biological target for antiproliferative activity. Based on the results of this screening, 5-benzylpaullones and paullone-9-carboxylic acid alkyl esters were developed as selective mMDH inhibitors. The new derivatives did not show noteworthy antiproliferative activity when tested on a panel of cancer cell lines, suggesting that mMDH inhibition is of minor relevance for the growth inhibition caused by paullones.
authors.affiliation: Technische Universität Braunschweig, Institut für Pharmazeutische Chemie, Beethovenstrasse 55, D-38106 Braunschweig, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Becker
authors.forename: Simone
authors.initials: S
authors.lastname: Kohfeld
authors.forename: Annette
authors.initials: A
authors.lastname: Lader
authors.forename: Lutz
authors.initials: L
authors.lastname: Preu
authors.forename: Tanja
authors.initials: T
authors.lastname: Pies
authors.forename: Karen
authors.initials: K
authors.lastname: Wieking
authors.forename: Yoan
authors.initials: Y
authors.lastname: Ferandin
authors.forename: Marie
authors.initials: M
authors.lastname: Knockaert
authors.forename: Laurent
authors.initials: L
authors.lastname: Meijer
authors.forename: Conrad
authors.initials: C
authors.lastname: Kunick
mesh_terms: D001552:Benzazepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000737:chemistry*; D045744:Cell Line, Tumor; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008291:Malate Dehydrogenase / Q000037:antagonists & inhibitors*; D008928:Mitochondria / Q000201:enzymology*; D013379:Substrate Specificity
chemical_list: D001552:Benzazepines; D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; C547599:paullone; D008291:Malate Dehydrogenase