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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Exploring DOXP-reductoisomerase binding limits using phosphonated N-aryl and N-heteroarylcarboxamides as DXR inhibitors
Bioorganic and Medicinal Chemistry, Volume 21, No. 14, Year 2013
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Description
DOXP-reductoisomerase (DXR) is a validated target for the development of antimalarial drugs to address the increase in resistant strains of Plasmodium falciparum. Series of aryl- and heteroarylcarbamoylphosphonic acids, their diethyl esters and disodium salts have been prepared as analogues of the potent DXR inhibitor fosmidomycin. The effects of the carboxamide N-substituents and the length of the methylene linker have been explored using in silico docking studies, saturation transfer difference NMR spectroscopy and enzyme inhibition assays using both EcDXR and PfDXR. These studies indicate an optimal linker length of two methylene units and have confirmed the importance of an additional binding pocket in the PfDXR active site. Insights into the constraints of the PfDXR binding site provide additional scope for the rational design of DXR inhibitors with increased ligand-receptor interactions. © 2013 Elsevier Ltd. All rights reserved.
Authors & Co-Authors
Bodill, Taryn
South Africa, Grahamstown
Rhodes University
Conibear, Anne C.
South Africa, Grahamstown
Rhodes University
Mutorwa, Marius K.
South Africa, Grahamstown
Rhodes University
Goble, Jessica L.
South Africa, Grahamstown
Rhodes University
Blatch, Gregory Lloyd
South Africa, Grahamstown
Rhodes University
Australia, Melbourne
Victoria University
Lobb, Kevin A.
South Africa, Grahamstown
Rhodes University
Klein, Rosalyn
South Africa, Grahamstown
Rhodes University
Kaye, Perry T.
South Africa, Grahamstown
Rhodes University
Statistics
Citations: 15
Authors: 8
Affiliations: 2
Identifiers
Doi:
10.1016/j.bmc.2013.04.076
ISSN:
09680896
e-ISSN:
14643391
Study Approach
Qualitative