Ainti-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)-α-l-rhamnopyranosyl]aucubin (scrolepidoside, 9) by spectroscopic means. The remaining metabolites were characterized as catalpol (1), 6-O-methylcatalpol (2), aucubin (3), 6-O-α-l-rhamnopyranosyl-aucubin (sinuatol, 4), 6-O-β-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 μg/ml). Except for 4, all pure compounds revealed some trypanocidal potential against Trypanosoma brucei rhodesiense (IC50 values 29.3–73.0 μg/ml). Only compound 10 showed moderate anti-plasmodial (IC50 40.6 μg/ml) and FabI enzyme inhibitory activity (IC50 100 μg/ml). 10 is the second natural product inhibiting the fatty acid biosynthesis of Plasmodium falciparum.