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.