The design of original antimalarial drugs. An example of phospholipid metabolism.
The aim of our program was to find an original chemotherapeutical treatment (and eventually a preventive treatment) of malaria, an illness largely predominant in developing countries, by interfering on an essential metabolism developed by Plasmodium during its erythrocytic phase. Apart from what has been learnt about metabolism and the pharmacological target, a crucial step has been taken during this contract by passing from micromolar in vitro active concentrations (during 1986-1990) to nanomolar ones (during 1990). These compounds should naturally short-circuit resistance phenomena already established against drugs in current use, as has already been verified on polypharmacoresistant strains or isolates of P. falciparum. The administration of a therapeutic dose of our molecules would now appear to be possible in all cases.
Vial
H J
HJ
Interactions membranaires, CNRS URA 530, Montpellier, France.
Ancelin
M L
ML
Elabbadi
N
N
Gumila
C
C
Bonnet
H
H
Jeong
Y H
YH
Philippot
J
J
Calas
M
M
Portefaix
P
P
Piquet
G
G
D000818:Animals; D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D002794:Choline / Q000378:metabolism; D004285:Dogs; D015195:Drug Design; D000882:Haplorhini; D008288:Malaria / Q000517:prevention & control; D026901:Membrane Transport Proteins; D051379:Mice; D008954:Models, Biological; D010743:Phospholipids / Q000378:metabolism*; D010961:Plasmodium / Q000187:drug effects* / Q000378:metabolism; D010962:Plasmodium berghei / Q000187:drug effects; D016788:Plasmodium chabaudi / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects; D013329:Structure-Activity Relationship
D000962:Antimalarials; D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D010743:Phospholipids; C065637:choline transporter; D002794:Choline