Bioassay-guided isolation of alkamides from an extract of Achillea ptarmica L. with antiprotozoal activity

In the course of an ongoing screening of the family Asteraceae for antiprotozoal activity [1], a CH₂Cl₂- extract from the flowering aerial parts of Achillea ptarmica L. (sneezewort yarrow) was active in vitro against Trypanosoma brucei rhodesiense (IC₅₀= 0.67 µg/mL) and Plasmodium falciparum (IC₅₀= 6.58 µg/mL).

Fig. 1

A bioassay guided fractionation by CC on silica followed by preparative HPLC led to the isolation and identification of five alkamides from the most active fractions. Pellitorine (1) and 8,9 Z-dehyropellitorine (2) are the main components of the extract. Beside these olefinic acid amides, four alkamides with diene-diyne structures (3 – 6) were isolated. Of these, 4 and 5 represented a mixture (2:1). Compounds 1-6 were tested for antiprotozoal activity in vitro (Table 1).

Tab. 1: In vitro antiprotozoal and cytotoxic activity of alkamides isolated from A. ptarmica. Data represent IC₅₀ values in µg/mL

Compound	T.b. rhodesiense (STIB 900)	P. falciparum (NF54)	L6 cells
1 (pellitorine)	5.35	3.25	45.0
2 (8,9 Z-dehydropellitorine)	2.00	6,47	16.5
	6.66
4+5 (2:1)	3.50	6,89	43.4
6 (anacycline)	5.12	under evaluation	47.6
Melarsoprol (pos. control)	0.002	–	-
Chloroquine (pos. control)	–	0.003
Podophyllotoxin (pos. control)	–		0.008

Pellitorine is the most active compound so far within this study against P. falciparum, while the 8,9-dehydro-derivative (2) is the most active compound against T. b. rhodesiense. None of these alkamides, however, was as active against T. b. rhodesiense as the crude extract so that more active constituents still remain to be identified.

References:

[1] Gökbulut A, et al. Planta Med, 78, 225 – 229 (2012).

This work is part of the activities of ResNetNPND: http://www.uni-muenster.de/ResNetNPND/