Design, synthesis and evaluation of novel uracil acetamide derivatives as potential inhibitors of Plasmodium falciparum dUTP nucleotidohydrolase

O McCarthy, A Musso-Buendia, M Kaiser…

Index: McCarthy, Orla; Musso-Buendia, Alex; Kaiser, Marcel; Brun, Reto; Ruiz-Perez, Luis M.; Johansson, Nils Gunnar; Pacanowska, Dolores Gonzalez; Gilbert, Ian H. European Journal of Medicinal Chemistry, 2009 , vol. 44, # 2 p. 678 - 688

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Citation Number: 38

Abstract

The ubiquitous enzyme dUTP nucleotidohydrolase (dUTPase) catalyses the hydrolysis of dUTP to dUMP and can be considered as the first line of defence against incorporation of uracil into DNA. Inhibition of this enzyme results in over-incorporation of uracil into DNA, leading to DNA fragmentation and cell death and is therefore lethal. By taking advantage of structural differences between the human and Plasmodium dUTPase, selective inhibitors ...

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