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PDBsum entry 3bar
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References listed in PDB file
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Key reference
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Title
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Structure-Activity relationships of c6-Uridine derivatives targeting plasmodia orotidine monophosphate decarboxylase.
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Authors
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A.M.Bello,
E.Poduch,
Y.Liu,
L.Wei,
I.Crandall,
X.Wang,
C.Dyanand,
K.C.Kain,
E.F.Pai,
L.P.Kotra.
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Ref.
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J Med Chem, 2008,
51,
439-448.
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PubMed id
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Abstract
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Malaria, caused by Plasmodia parasites, has re-emerged as a major problem,
imposing its fatal effects on human health, especially due to multidrug
resistance. In Plasmodia, orotidine 5'-monophosphate decarboxylase (ODCase) is
an essential enzyme for the de novo synthesis of uridine 5'-monophosphate.
Impairing ODCase in these pathogens is a promising strategy to develop novel
classes of therapeutics. Encouraged by our recent discovery that 6-iodo uridine
is a potent inhibitor of P. falciparum, we investigated the structure-activity
relationships of various C6 derivatives of UMP. 6-Cyano, 6-azido, 6-amino,
6-methyl, 6- N-methylamino, and 6- N, N-dimethylamino derivatives of uridine
were evaluated against P. falciparum. The mononucleotides of 6-cyano, 6-azido,
6-amino, and 6-methyl uridine derivatives were studied as inhibitors of
plasmodial ODCase. 6-Azidouridine 5'-monophosphate is a potent covalent
inhibitor of P. falciparum ODCase. 6-Methyluridine exhibited weak antimalarial
activity against P. falciparum 3D7 isolate. 6- N-Methylamino and 6- N,
N-dimethylamino uridine derivatives exhibited moderate antimalarial activities.
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