Anti-malarial drug targets: screening for inhibitors of 2C-methyl-D-erythritol 4-phosphate synthase (IspC protein) in Mediterranean plants.
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.
Kaiser
J
J
Lehrstuhl für Organische Chemie und Biochemie, Technische Universität München, Lichtenbergstr. 4, D-85747 Garching, Germany.
Yassin
M
M
Prakash
S
S
Safi
N
N
Agami
M
M
Lauw
S
S
Ostrozhenkova
E
E
Bacher
A
A
Rohdich
F
F
Eisenreich
W
W
Safi
J
J
Golan-Goldhirsh
A
A
D019747:Aldose-Ketose Isomerases / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D000595:Amino Acid Sequence; D000818:Animals; D000962:Antimalarials / Q000737:chemistry*; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy; D019083:Mediterranean Region; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry*; D018515:Plant Leaves; D010946:Plants, Medicinal; D010963:Plasmodium falciparum / Q000201:enzymology* / Q000235:genetics
D000962:Antimalarials; D009097:Multienzyme Complexes; D010936:Plant Extracts; D010088:Oxidoreductases; C114231:1-deoxy-D-xylulose 5-phosphate reductoisomerase; D019747:Aldose-Ketose Isomerases