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Thiazolopyrimidine Inhibitors of 2‐Methylerythritol 2,4‐Cyclodiphosphate Synthase (IspF) from Mycobacterium tuberculosis and Plasmodium falciparum
Author(s) -
Geist Julie G.,
Lauw Susan,
Illarionova Victoria,
Illarionov Boris,
Fischer Markus,
Gräwert Tobias,
Rohdich Felix,
Eisenreich Wolfgang,
Kaiser Johannes,
Groll Michael,
Scheurer Christian,
Wittlin Sergio,
AlonsoGómez José L.,
Schweizer W. Bernd,
Bacher Adelbert,
Diederich François
Publication year - 2010
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201000083
Subject(s) - plasmodium falciparum , mycobacterium tuberculosis , atp synthase , arabidopsis thaliana , biology , in vitro , chemistry , tuberculosis , biochemistry , microbiology and biotechnology , enzyme , malaria , immunology , medicine , gene , mutant , pathology
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.