Design and synthesis of amidoxime derivatives for orally potent C-alkylamidine-based antimalarial agents.
Within the frame of the design of prodrug candidates to deliver a C-alkylamidine antimalarial agent, we showed that specific O-substitutions were needed on the alkylamidoxime structure. Among the newly synthesized molecules, bis-oxadiazolone and bis-O-methylsulfonylamidoxime derivatives induced a complete clearance of parasitemia in mice after oral administration.
Ouattara
Mahama
M
Institut des Biomolécules Max Mousseron, UMR 5247, CNRS - Université Montpellier I - Université Montpellier II, 34093 Montpellier, France.
Wein
Sharon
S
Denoyelle
Séverine
S
Ortial
Stéphanie
S
Durand
Thierry
T
Escale
Roger
R
Vial
Henri
H
Vo-Hoang
Yen
Y
D000284:Administration, Oral; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D008288:Malaria / Q000188:drug therapy*; D051379:Mice; D008956:Models, Chemical; D018512:Parasitemia / Q000188:drug therapy*; D010963:Plasmodium falciparum; D011355:Prodrugs
D000962:Antimalarials; D000975:Antioxidants; D011355:Prodrugs