title: Exploring new inhibitors of Plasmodium falciparum purine nucleoside phosphorylase.
abstract: Plasmodium falciparum purine nucleoside phosphorylase (PfPNP) has a central role in purine salvage and inhibitors of the enzyme have been shown to have antiplasmodial activity. The enzyme preferentially uses inosine as substrate (K(m)=5 μM, k(cat)/K(m)=7.4×10(4) M(-1) s(-1)), but can also use uridine, albeit less efficiently (K(m)=85 μM, k(cat)/K(m)=306 M(-1) s(-1)). In an effort to identify new PfPNP inhibitors, two series of compounds were prepared. Series 1 was based on known human uridine phosphorylase inhibitors whilst series 2 was uracil equivalents of purine-based PNP transition state inhibitors. These two series of compounds were assayed for inhibition of both PfPNP activity and growth of P. falciparum. The transition state analogues were found to be moderate inhibitors of PfPNP (most potent compound, K(i)=6 μM).
authors.affiliation: Instituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones Científicas, Avda. del Conocimiento s/n, 18100-Armilla, Granada, Spain.
authors.forename: Huaqing
authors.initials: H
authors.lastname: Cui
authors.forename: Gian Filippo
authors.initials: GF
authors.lastname: Ruda
authors.forename: Juana
authors.initials: J
authors.lastname: Carrero-Lérida
authors.forename: Luis M
authors.initials: LM
authors.lastname: Ruiz-Pérez
authors.forename: Ian H
authors.initials: IH
authors.lastname: Gilbert
authors.forename: Dolores
authors.initials: D
authors.lastname: González-Pacanowska
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010963:Plasmodium falciparum / Q000201:enzymology*; D011683:Purine-Nucleoside Phosphorylase / Q000037:antagonists & inhibitors*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D004791:Enzyme Inhibitors; D011683:Purine-Nucleoside Phosphorylase