Synthesis and antimalarial activity of new atovaquone derivatives.
In this paper we describe the design and synthesis of 18 derivatives of the antimicrobial atovaquone which were substituted at the 3-hydroxy group by ester and ether functions. The compounds were evaluated in vitro for their activity against the growth of Plasmodium falciparum, the malaria causing parasite. All the compounds showed potent activity, with IC(50) values in the range of 1.25-50 nM, comparable to those of atovaquone and much higher than chloroquine or quinine.
El Hage
Salomé
S
Université Paul Sabatier Toulouse III, Faculté de Pharmacie, Laboratoire de Chimie Pharmaceutique, 31062 Toulouse Cedex 09, France.
Ane
Michèle
M
Stigliani
Jean-Luc
JL
Marjorie
Maynadier
M
Vial
Henri
H
Baziard-Mouysset
Geneviève
G
Payard
Marc
M
D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D053626:Atovaquone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D016778:Malaria, Falciparum / Q000188:drug therapy*; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000962:Antimalarials; D053626:Atovaquone