- Title
- Exploring DOXP-reductoisomerase binding limits using phosphonated N-aryl and N-heteroarylcarboxamides as DXR inhibitors
- Creator
- Bodill, Taryn, Conibear, Anne C, Mutorwa, Marius K M, Goble, Jessica L, Blatch, Gregory L, Lobb, Kevin A, Klein, Rosalyn, Kaye, Perry T
- Subject
- To be catalogued
- Date
- 2013
- Type
- text
- Type
- article
- Identifier
- http://hdl.handle.net/10962/448912
- Identifier
- vital:74770
- Identifier
- xlink:href=""
- 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.
- Format
- computer, online resource, application/pdf, 1 online resource (10 pages), pdf
- Publisher
- Elsevier
- Language
- English
- Relation
- Bioorganic and Medicinal Chemistry, Bodill, T., Conibear, A.C., Mutorwa, M.K., Goble, J.L., Blatch, G.L., Lobb, K.A., Klein, R. and Kaye, P.T., 2013. Exploring DOXP-reductoisomerase binding limits using phosphonated N-aryl and N-heteroarylcarboxamides as DXR inhibitors. Bioorganic and medicinal chemistry, 21(14), pp.4332-4341, Bioorganic and Medicinal Chemistry volume 21 number 14 p. 4332 2013 0968-0896
- Rights
- Publisher
- Rights
- Use of this resource is governed by the terms and conditions of the Elsevier Terms and Conditions Statement (https://www.elsevier.com/legal/elsevier-website-terms-and-conditions)
- Rights
- Closed Access
- Hits: 21
- Visitors: 19
- Downloads: 0
Collections
Klein, Rosalyn (Assoc Prof)
RU Centre for Chemico- and Biomedicinal Research (CCBR)
Kaye, Perry T (Distinguished Fellow Emeritus Professor)
Blatch, Gregory Lloyd (Prof)
Lobb, Kevin Allan (Assoc Prof)
SDG 03. Good Health and Well-Being
RU Department of Chemistry
RU Department of Biochemistry, Microbiology and Bioinformatics
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details | SOURCE1 | Exploring DOXP-reductoisomerase binding limits using phosphonated N-aryl and N-heteroarylcarboxamides as DXR inhibitors.pdf | 771 KB | Adobe Acrobat PDF | View Details |