title: Synthesis and evaluation of phosphonated N-heteroarylcarboxamides as DOXP-reductoisomerase (DXR) inhibitors.
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.
authors.affiliation: Centre for Chemico- and Biomedicinal Research, Rhodes University, Grahamstown 6140, South Africa.
authors.forename: Taryn
authors.initials: T
authors.lastname: Bodill
authors.forename: Anne C
authors.initials: AC
authors.lastname: Conibear
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Blatch
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Lobb
authors.forename: Perry T
authors.initials: PT
authors.lastname: Kaye
mesh_terms: D019747:Aldose-Ketose Isomerases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D003198:Computer Simulation; D015195:Drug Design; D005578:Fosfomycin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010088:Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011485:Protein Binding
chemical_list: D000962:Antimalarials; D005663:Furans; D009097:Multienzyme Complexes; D063065:Organophosphonates; C560497:diethyl 2-((furan-2-ylmethyl)carbamoyl)ethylphosphonate; D005578:Fosfomycin; C024640:fosmidomycin; D010088:Oxidoreductases; C114231:1-deoxy-D-xylulose 5-phosphate reductoisomerase; D019747:Aldose-Ketose Isomerases