The ethanolic root extract of Scrophidaria lepidota, an endemic plant of the Turkish flora, has been investigated for its anti-protozoal and inhibitory effect towards plasmodial enoyl-ACP reductase (Fab1), 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 mug/ml). Except for 4, all pure compounds revealed some trypanocidal potential against Trypanosoma brucei rhodesiense (IC50 values 29.3-73.0 mug/ml). Only compound 10 showed moderate anti-plasmodial (IC50 40.6 mug/ml) and FabI enzyme inhibitory activity (IC50 100 mug/ml). 10 is the second natural product inhibiting the fatty acid biosynthesis of Plasmodium falciparum. (C) 2004 Elsevier Ltd. All rights reserved.