Artemisinin-dipeptidyl vinyl sulfone hybrid molecules: design, synthesis and preliminary SAR for antiplasmodial activity and falcipain-2 inhibition.
A series of artemisinin-vinyl sulfone hybrid molecules with the potential to act in the parasite food vacuole via endoperoxide activation and falcipain inhibition was synthesized and screened for antiplasmodial activity and falcipain-2 inhibition. All conjugates were active against the Plasmodium falciparum W2 strain in the low nanomolar range and those containing the Leu-hPhe core inhibited falcipain-2 in low micromolar range.
iMed.UL, Faculty of Pharmacy, University of Lisbon, Av Prof. Gama Pinto, 1649-003, Portugal.
Rita
R
Capela
Rudi
R
Oliveira
Lídia M
LM
Gonçalves
Ana
A
Domingos
Jiri
J
Gut
Philip J
PJ
Rosenthal
Francisca
F
Lopes
Rui
R
Moreira
D000818:Animals; D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology; D037621:Artemisinins / Q000737:chemistry* / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000187:drug effects*; D004151:Dipeptides / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000737:chemistry* / Q000494:pharmacology
D000962:Antimalarials; D000981:Antiprotozoal Agents; D037621:Artemisinins; D004151:Dipeptides; D013450:Sulfones; C009873:divinyl sulfone; D003546:Cysteine Endopeptidases; C416224:falcipain 2