1. Anti-malarial drug targets: screening for inhibitors of 2C-methyl-D-erythritol 4-phosphate synthase (IspC protein) in Mediterranean plants.
- Author
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Kaiser J, Yassin M, Prakash S, Safi N, Agami M, Lauw S, Ostrozhenkova E, Bacher A, Rohdich F, Eisenreich W, Safi J, and Golan-Goldhirsh A
- Subjects
- Amino Acid Sequence, Animals, Escherichia coli genetics, Humans, Malaria, Falciparum drug therapy, Mediterranean Region, Molecular Sequence Data, Plant Leaves, Plasmodium falciparum genetics, Aldose-Ketose Isomerases antagonists & inhibitors, Aldose-Ketose Isomerases chemistry, Antimalarials chemistry, Escherichia coli enzymology, Multienzyme Complexes antagonists & inhibitors, Multienzyme Complexes chemistry, Oxidoreductases antagonists & inhibitors, Oxidoreductases chemistry, Phytotherapy, Plant Extracts chemistry, Plants, Medicinal, Plasmodium falciparum enzymology
- Abstract
The recently discovered non-mevalonate pathway of isoprenoid biosynthesis serves as the unique source of terpenoids in numerous pathogenic eubacteria and in apicoplast-type protozoa, most notably Plasmodium, but is absent in mammalian cells. It is therefore an attractive target for anti-infective chemotherapy. The first committed step of the non-mevalonate pathway is catalyzed by 2C-methyl-D-erythritol 4-phosphate synthase (IspC). Using photometric and NMR spectroscopic assays, we screened extracts of Mediterranean plants for inhibitors of the enzyme. Strongest inhibitory activity was found in leaf extracts of Cercis siliquastrum.
- Published
- 2007
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