Development of 5-benzylpaullones and paullone-9-carboxylic acid alkyl esters as selective inhibitors of mitochondrial malate dehydrogenase (mMDH).
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.
Becker
Anja
A
Technische Universität Braunschweig, Institut für Pharmazeutische Chemie, Beethovenstrasse 55, D-38106 Braunschweig, Germany.
Kohfeld
Simone
S
Lader
Annette
A
Preu
Lutz
L
Pies
Tanja
T
Wieking
Karen
K
Ferandin
Yoan
Y
Knockaert
Marie
M
Meijer
Laurent
L
Kunick
Conrad
C
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
D001552:Benzazepines; D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; C547599:paullone; D008291:Malate Dehydrogenase