Plasmepsin II inhibition and antiplasmodial activity of Primaquine-Statine 'double-drugs'.
Statine-based inhibitors of Plasmepsin II (PLMII) coupled with Primaquine have been designed using the 'double-drug' approach. The IC50 values for PLMII inhibition ranged from 0.59 to 400 nM and the best IC50 value for inhibition of Plasmodium falciparum growth in vitro was 0.4 microM, which represent a remarkable improvement compared to other statine-based PLMII inhibitors.
Romeo
Sergio
S
Institute of Medicinal Chemistry, University of Milan, Viale Abruzzi 42, 20131 Milan, Italy. sergio.romeo@unimi.it
Dell'Agli
Mario
M
Parapini
Silvia
S
Rizzi
Luca
L
Galli
Germana
G
Mondani
Monica
M
Sparatore
Anna
A
Taramelli
Donatella
D
Bosisio
Enrica
E
D000596:Amino Acids / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D002738:Chloroquine; D003432:Cross-Linking Reagents; D015195:Drug Design; D004351:Drug Resistance; D004912:Erythrocytes / Q000382:microbiology; D006801:Humans; D020128:Inhibitory Concentration 50; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology; D011319:Primaquine / Q000737:chemistry* / Q000494:pharmacology; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D015800:Protozoan Proteins; D013329:Structure-Activity Relationship
D000596:Amino Acids; D000962:Antimalarials; D003432:Cross-Linking Reagents; D011480:Protease Inhibitors; D015800:Protozoan Proteins; D002738:Chloroquine; D016282:Aspartic Acid Endopeptidases; C100637:plasmepsin II; D011319:Primaquine; C013165:statine