Exploring new inhibitors of Plasmodium falciparum purine nucleoside phosphorylase.

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Cui H, Ruda GF, Carrero-Lerida J, Ruiz-Perez LM, Gilbert IH, Gonzalez-Pacanowska D

Exploring new inhibitors of Plasmodium falciparum purine nucleoside phosphorylase.

Eur J Med Chem. 2010 Nov;45(11):5140-9. doi: 10.1016/j.ejmech.2010.08.026. Epub 2010 Aug 14.

PubMed ID

20817362 [ View in PubMed

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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 muM, k(cat)/K(m)=7.4x10(4) M(-1) s(-1)), but can also use uridine, albeit less efficiently (K(m)=85 muM, 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 muM).

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Forodesine	Purine nucleoside phosphorylase	Kd (nM)	0.056	N/A	N/A	Details