title: Reverse fosmidomycin derivatives against the antimalarial drug target IspC (Dxr).
abstract: Reverse hydroxamate-based inhibitors of IspC, a key enzyme of the non-mevalonate pathway of isoprenoid biosynthesis and a validated antimalarial target, were synthesized and biologically evaluated. The binding mode of one derivative in complex with EcIspC and a divalent metal ion was clarified by X-ray analysis. Pilot experiments have demonstrated in vivo potential.
authors.affiliation: Institut für Pharmazeutische und Medizinische Chemie, Heinrich Heine Universität, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
authors.forename: Christoph T
authors.initials: CT
authors.lastname: Behrendt
authors.forename: Andrea
authors.initials: A
authors.lastname: Kunfermann
authors.forename: Victoria
authors.initials: V
authors.lastname: Illarionova
authors.forename: An
authors.initials: A
authors.lastname: Matheeussen
authors.forename: Miriam K
authors.initials: MK
authors.lastname: Pein
authors.forename: Tobias
authors.initials: T
authors.lastname: Gräwert
authors.forename: Johannes
authors.initials: J
authors.lastname: Kaiser
authors.forename: Adelbert
authors.initials: A
authors.lastname: Bacher
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Eisenreich
authors.forename: Boris
authors.initials: B
authors.lastname: Illarionov
authors.forename: Markus
authors.initials: M
authors.lastname: Fischer
authors.forename: Louis
authors.initials: L
authors.lastname: Maes
authors.forename: Michael
authors.initials: M
authors.lastname: Groll
authors.forename: Thomas
authors.initials: T
authors.lastname: Kurz
mesh_terms: D019747:Aldose-Ketose Isomerases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology; D005578:Fosfomycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008288:Malaria / Q000188:drug therapy; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors* / Q000737:chemistry; D010088:Oxidoreductases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D021261:Parasitic Sensitivity Tests; D010962:Plasmodium berghei; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D009097:Multienzyme Complexes; D005578:Fosfomycin; C024640:fosmidomycin; D010088:Oxidoreductases; C114231:1-deoxy-D-xylulose 5-phosphate reductoisomerase; D019747:Aldose-Ketose Isomerases