Synthesis and evaluation of non-peptidic cysteine protease inhibitors of P. falciparum derived from etacrynic acid.
A series of etacrynic acid derivatives was synthesized and screened for their in vitro activity against Plasmodium falciparum, as well as their activity against recombinantly expressed falcipain-2 and -3. The two most active compounds of the series displayed IC(50) values of 9.0 and 18.8 microM against Plasmodia.
Dude
Marie-Adrienne
MA
Research Center for Infectious Diseases, University of Würzburg, Röntgenring 11, 97070 Würzburg, Germany. adrienne.dude@uni-wuerzburg.de
Kaeppler
Ulrich
U
Herb
Monika
M
Schiller
Markus
M
Schulz
Franziska
F
Vedder
Birgit
B
Heppner
Saskia
S
Pradel
Gabriele
G
Gut
Jiri
J
Rosenthal
Philip J
PJ
Schirmeister
Tanja
T
Leippe
Matthias
M
Gelhaus
Christoph
C
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D003546:Cysteine Endopeptidases / Q000187:drug effects* / Q000235:genetics; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004976:Ethacrynic Acid / Q000031:analogs & derivatives*; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000235:genetics
D000962:Antimalarials; D015853:Cysteine Proteinase Inhibitors; D011994:Recombinant Proteins; D003546:Cysteine Endopeptidases; C416224:falcipain 2; C443101:falcipain 3; D004976:Ethacrynic Acid