Abstract
Previously we have shown that trityl and diphenyl deoxyuridine derivatives and their acyclic analogues can inhibit Plasmodium falciparum dUTPase (PfdUTPase). We report the synthesis of conformationally restrained amide derivatives as inhibitors PfdUTPase, including both acyclic and cyclic examples. Activity was dependent on the orientation and location of the amide constraining group. In the case of the acyclic series, we were able to obtain amide-constrained analogues which showed similar or greater potency than the unconstrained analogues. Unfortunately these compounds showed lower selectivity in cellular assays.
Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Amides / chemistry
-
Antimalarials / chemical synthesis
-
Antimalarials / chemistry*
-
Antimalarials / metabolism
-
Enzyme Inhibitors / chemical synthesis
-
Enzyme Inhibitors / chemistry*
-
Enzyme Inhibitors / metabolism
-
Kinetics
-
Nucleosides / chemical synthesis
-
Nucleosides / chemistry*
-
Nucleosides / metabolism
-
Plasmodium falciparum / enzymology*
-
Protein Binding
-
Protozoan Proteins / antagonists & inhibitors*
-
Protozoan Proteins / metabolism
-
Pyrophosphatases / antagonists & inhibitors*
-
Pyrophosphatases / metabolism
-
Uridine / chemistry
Substances
-
Amides
-
Antimalarials
-
Enzyme Inhibitors
-
Nucleosides
-
Protozoan Proteins
-
Pyrophosphatases
-
dUTP pyrophosphatase
-
Uridine