Anti-protozoal and plasmodial FabI enzyme inhibiting metabolites of Scrophularia lepidota roots

Phytochemistry. 2005 Feb;66(3):355-62. doi: 10.1016/j.phytochem.2004.11.013.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiprotozoal Agents / chemistry
  • Antiprotozoal Agents / isolation & purification*
  • Antiprotozoal Agents / pharmacology*
  • Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Oxidoreductases / antagonists & inhibitors*
  • Oxidoreductases / metabolism
  • Plant Roots / chemistry*
  • Plant Roots / metabolism
  • Plasmodium / drug effects*
  • Plasmodium / enzymology*
  • Scrophularia / chemistry*
  • Scrophularia / metabolism

Substances

  • Antiprotozoal Agents
  • Enzyme Inhibitors
  • Oxidoreductases
  • Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)