title: Thiazolopyrimidine inhibitors of 2-methylerythritol 2,4-cyclodiphosphate synthase (IspF) from Mycobacterium tuberculosis and Plasmodium falciparum.
abstract: A library of 40,000 compounds was screened for inhibitors of 2-methylerythritol 2,4-cyclodiphosphate synthase (IspF) protein from Arabidopsis thaliana using a photometric assay. A thiazolopyrimidine derivative resulting from the high-throughput screen was found to inhibit the IspF proteins of Mycobacterium tuberculosis, Plasmodium falciparum, and A. thaliana with IC(50) values in the micromolar range. Synthetic efforts afforded derivatives that inhibit IspF protein from M. tuberculosis and P. falciparum with IC(50) values in the low micromolar range. Several compounds act as weak inhibitors in the P. falciparum red blood cell assay.
authors.affiliation: Laboratorium für Organische Chemie, ETH Zürich, Hönggerberg, HCI, 8093 Zürich, Switzerland.
authors.forename: Julie G
authors.initials: JG
authors.lastname: Geist
authors.forename: Susan
authors.initials: S
authors.lastname: Lauw
authors.forename: Victoria
authors.initials: V
authors.lastname: Illarionova
authors.forename: Boris
authors.initials: B
authors.lastname: Illarionov
authors.forename: Markus
authors.initials: M
authors.lastname: Fischer
authors.forename: Tobias
authors.initials: T
authors.lastname: Gräwert
authors.forename: Felix
authors.initials: F
authors.lastname: Rohdich
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Eisenreich
authors.forename: Johannes
authors.initials: J
authors.lastname: Kaiser
authors.forename: Michael
authors.initials: M
authors.lastname: Groll
authors.forename: Christian
authors.initials: C
authors.lastname: Scheurer
authors.forename: Sergio
authors.initials: S
authors.lastname: Wittlin
authors.forename: José L
authors.initials: JL
authors.lastname: Alonso-Gómez
authors.forename: W Bernd
authors.initials: WB
authors.lastname: Schweizer
authors.forename: Adelbert
authors.initials: A
authors.lastname: Bacher
authors.forename: François
authors.initials: F
authors.lastname: Diederich
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017360:Arabidopsis / Q000201:enzymology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008968:Molecular Conformation; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D019761:Phosphorus-Oxygen Lyases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010963:Plasmodium falciparum / Q000201:enzymology*; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D000962:Antimalarials; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D015800:Protozoan Proteins; D011743:Pyrimidines; D011994:Recombinant Proteins; D054852:Small Molecule Libraries; D019761:Phosphorus-Oxygen Lyases; C512265:IspF protein, Arabidopsis