title: Anti-protozoal and plasmodial FabI enzyme inhibiting metabolites of Scrophularia lepidota roots.
abstract: 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.
authors.affiliation: Institute of Organic Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland. deniz@oci.unizh.ch
authors.forename: Deniz
authors.initials: D
authors.lastname: Tasdemir
authors.forename: Nadide Deniz
authors.initials: ND
authors.lastname: Güner
authors.forename: Remo
authors.initials: R
authors.lastname: Perozzo
authors.forename: Reto
authors.initials: R
authors.lastname: Brun
authors.forename: Ali A
authors.initials: AA
authors.lastname: Dönmez
authors.forename: Ihsan
authors.initials: I
authors.lastname: Calis
authors.forename: Peter
authors.initials: P
authors.lastname: Rüedi
mesh_terms: 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
chemical_list: D000981:Antiprotozoal Agents; D004791:Enzyme Inhibitors; D010088:Oxidoreductases; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)