Synthesis of quinolinyl chalcones and evaluation of their antimalarial activity.
Quinolinyl chalcones were synthesized and evaluated for their inhibition of the Plasmodium falciparum cystein protease falcipain and their activity against cultured P. falciparum parasites. They were also tested for in vivo efficacy in a rodent P. berghei model. Their activity against falcipain and as antimalarials was moderate, but antimalarial activity was probably not due to the inhibition of falcipain and may follow a different mechanism. 1-(2,4-Dichlorophenyl)-3-[3-(2-chloro-6,7-dimethoxiquinolinyl)]-2-propen-1-one 3j was the most promising compound among those here reported (IC50 19.0 microM).
Domínguez
J N
JN
Laboratorio de Síntesis Orgánica, Facultad de Farmacia, Universidad Central de Venezuela, 1051, Caracas, Venezuela. dominguj@camelot.rect.ucv.ve
Charris
J E
JE
Lobo
G
G
Gamboa de Domínguez
N
N
Moreno
M M
MM
Riggione
F
F
Sanchez
E
E
Olson
J
J
Rosenthal
P J
PJ
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002599:Chalcone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D010450:Endopeptidases / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D008288:Malaria / Q000188:drug therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010962:Plasmodium berghei / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects; D015363:Quinolones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D013329:Structure-Activity Relationship
D000962:Antimalarials; D015363:Quinolones; D002599:Chalcone; D010450:Endopeptidases