In vitro antileishmanial activity of fluoro-artemisinin derivatives against Leishmania donovani.
The antileishmanial activity of 19 fluoro-artemisinin derivatives was evaluated in vitro against the promastigote forms of Leishmania donovani. The most active compound BB 201, an amino derivative, exhibited an IC50 at about 1microM and no cross-resistance was found on miltefosine-resistant and sitamaquine-resistant lines. Despite these promising data, no activity was observed on intramacrophage amastigote stage. Although the membranes that have to be crossed by the compounds and pH conditions between intraerythrocyte Plasmodium and intramacrophage Leishmania have similarities, the targets affected by artemisinin derivatives in promastigotes could be differentially expressed in amastigotes.
Chollet
Constance
C
Molécules Fluorées et Chimie Médicinale, UMR 8076 CNRS, IFR 141, Faculté de Pharmacie, Univ Paris-Sud, Rue Jean-Baptiste Clément, F-92290 Châtenay-Malabry, France.
Crousse
Benoît
B
Bories
Christian
C
Bonnet-Delpon
Danièle
D
Loiseau
Philippe M
PM
D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D000977:Antiparasitic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D037621:Artemisinins / Q000737:chemistry / Q000494:pharmacology*; D004351:Drug Resistance; D004912:Erythrocytes / Q000469:parasitology; D007202:Indicators and Reagents; D007893:Leishmania donovani / Q000187:drug effects* / Q000254:growth & development; D008264:Macrophages / Q000469:parasitology; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000494:pharmacology
D000634:Aminoquinolines; D000977:Antiparasitic Agents; D037621:Artemisinins; D007202:Indicators and Reagents; D010767:Phosphorylcholine; C039128:miltefosine; C031327:artemisinin; C080436:8-aminoquinoline