Synthesis and evaluation of phosphonated N-heteroarylcarboxamides as DOXP-reductoisomerase (DXR) inhibitors |
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Authors: | Bodill Taryn Conibear Anne C Blatch Gregory L Lobb Kevin A Kaye Perry T |
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Affiliation: | Centre for Chemico- and Biomedicinal Research, Rhodes University, Grahamstown 6140, South Africa. |
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Abstract: | The diethyl esters and disodium salts of a range of heteroarylcarbamoylphosphonic acids have been prepared and evaluated as analogues of the highly active DOXP-reductoisomerase (DXR) inhibitor, fosmidomycin. Computer-simulated docking studies, Saturation Transfer Difference (STD) NMR analysis and enzyme inhibition assays have been used to explore enzyme-binding and -inhibition potential, while in silico analysis of the DXR active site has highlighted the importance of including a well-parameterised metal co-factor in docking studies and has revealed the availability of an additional binding pocket to guide future drug design. |
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