title: Synthetic Fosmidomycin analogues with altered chelating moieties do not inhibit 1-deoxy-d-xylulose 5-phosphate Reductoisomerase or Plasmodium falciparum growth in vitro.
abstract: Fourteen new fosmidomycin analogues with altered metal chelating groups were prepared and evaluated for inhibition of E. coli Dxr, M. tuberculosis Dxr and the growth of P. falciparum K1 in human erythrocytes. None of the synthesized compounds showed activity against either enzyme or the Plasmodia. This study further underlines the importance of the hydroxamate functionality and illustrates that identifying effective alternative bidentate ligands for this target enzyme is challenging.
authors.affiliation: Laboratory for Medicinal Chemistry, Ghent University, Harelbekestraat 72, Ghent B-9000, Belgium. rene.chofor@ugent.be.
authors.forename: René
authors.initials: R
authors.lastname: Chofor
authors.affiliation: Laboratory for Medicinal Chemistry, Ghent University, Harelbekestraat 72, Ghent B-9000, Belgium. martijn.risseeuw@ugent.be.
authors.forename: Martijn D P
authors.initials: MD
authors.lastname: Risseeuw
authors.affiliation: Department of Chemistry, University of Namur, UNamur, Rue de Bruxelles 61, Namur B-5000, Belgium. jenny.pouyez@unamur.be.
authors.forename: Jenny
authors.initials: J
authors.lastname: Pouyez
authors.affiliation: Department of Chemistry and Biochemistry, George Mason University, Manassas, VA 20110, USA. cjohny@gmu.edu.
authors.forename: Chinchu
authors.initials: C
authors.lastname: Johny
authors.affiliation: Department of Chemistry, University of Namur, UNamur, Rue de Bruxelles 61, Namur B-5000, Belgium. johan.wouters@unamur.be.
authors.forename: Johan
authors.initials: J
authors.lastname: Wouters
authors.affiliation: Department of Chemistry, George Washington University, Washington, DC 20052, USA. cdowd@gwu.edu.
authors.forename: Cynthia S
authors.initials: CS
authors.lastname: Dowd
authors.affiliation: Department of Chemistry and Biochemistry, George Mason University, Manassas, VA 20110, USA. rcouch@gmu.edu.
authors.forename: Robin D
authors.initials: RD
authors.lastname: Couch
authors.affiliation: Laboratory for Medicinal Chemistry, Ghent University, Harelbekestraat 72, Ghent B-9000, Belgium. serge.vancalenbergh@ugent.be.
authors.forename: Serge
authors.initials: S
authors.lastname: Van Calenbergh
mesh_terms: D019747:Aldose-Ketose Isomerases / Q000037:antagonists & inhibitors; D000962:Antimalarials / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000737:chemistry; D004912:Erythrocytes / Q000187:drug effects*; D005578:Fosfomycin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D006801:Humans; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development
chemical_list: D000962:Antimalarials; D004791:Enzyme Inhibitors; D005578:Fosfomycin; C024640:fosmidomycin; C114231:1-deoxy-D-xylulose 5-phosphate reductoisomerase; D019747:Aldose-Ketose Isomerases