Probing structure/affinity relationships for the Plasmodium falciparum hexose transporter with glucose derivatives.
A series of 3-O-substituted glucose derivatives was prepared with alkyl, alkenyl, aromatic and ferrocenic substituents; to vary lipophilicity and hydrogen bonding ethylenedioxy and perfluorinated fragments were also introduced. Apparent affinities for the Plasmodium falciparum hexose transporter (PfHT) were determined after heterologous expression in Xenopus oocytes, with highest affinities for compounds with C8-C13 lipophilic chains. As no derivatives show significant affinity for the mammalian glucose transporter (GLUT1), these structure/affinity assays contribute to design of potent PfHT inhibitors and eventual development of antimalarials.
Fayolle
Martine
M
Laboratoire d'Etudes Dynamiques et Structurales de la Sélectivité (LEDSS), UMR 5616 (IFR 2607), Université Joseph Fourier Grenoble 1, 38402 St Martin d'Hères, France.
Ionita
Marina
M
Krishna
Sanjeev
S
Morin
Christophe
C
Patel
Asha Parbhu
AP
D000818:Animals; D001692:Biological Transport; D005947:Glucose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D009004:Monosaccharide Transport Proteins / Q000737:chemistry* / Q000378:metabolism*; D009865:Oocytes; D010963:Plasmodium falciparum / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014981:Xenopus
D009004:Monosaccharide Transport Proteins; D005947:Glucose