Anti-protozoal and plasmodial FabI enzyme inhibiting metabolites of Scrophularia lepidota roots.
The ethanolic root extract of Scrophularia lepidota, an endemic plant of the Turkish flora, has been investigated for its anti-protozoal and inhibitory effect towards plasmodial enoyl-ACP reductase (FabI), a key enzyme of fatty acid biosynthesis in Plasmodium falciparum. Chromatographic separation of the extract yielded 10 iridoids (1-10), two of which are new, and a known phenylethanoid glycoside (11). The structures of the new compounds were determined as 3,4-dihydro-methylcatalpol (8) and 6-O-[4''-O-trans-(3,4-dimethoxycinnamoyl)-alpha-L-rhamnopyranosyl]aucubin (scrolepidoside, 9) by spectroscopic means. The remaining metabolites were characterized as catalpol (1), 6-O-methylcatalpol (2), aucubin (3), 6-O-alpha-L-rhamnopyranosyl-aucubin (sinuatol, 4), 6-O-beta-D-xylopyranosylaucubin (5), ajugol (6), ajugoside (7), an iridoid-related aglycone (10) and angoroside C (11). Nine isolates were active against Leishmania donovani, with the new compound 9 being most potent (IC50 6.1 microg/ml). Except for 4, all pure compounds revealed some trypanocidal potential against Trypanosoma brucei rhodesiense (IC50 values 29.3-73.0 microg/ml). Only compound 10 showed moderate anti-plasmodial (IC50 40.6 microg/ml) and FabI enzyme inhibitory activity (IC50 100 microg/ml). 10 is the second natural product inhibiting the fatty acid biosynthesis of Plasmodium falciparum.
Tasdemir
Deniz
D
Institute of Organic Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland. deniz@oci.unizh.ch
Güner
Nadide Deniz
ND
Perozzo
Remo
R
Brun
Reto
R
Dönmez
Ali A
AA
Calis
Ihsan
I
Rüedi
Peter
P
D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH); D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010088:Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018517:Plant Roots / Q000737:chemistry* / Q000378:metabolism; D010961:Plasmodium / Q000187:drug effects* / Q000201:enzymology*; D032266:Scrophularia / Q000737:chemistry* / Q000378:metabolism
D000981:Antiprotozoal Agents; D004791:Enzyme Inhibitors; D010088:Oxidoreductases; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)