Alkamides from Anacyclus pyrethrum L. and Their in Vitro Antiprotozoal Activity

In our ongoing study to evaluate the antiprotozoal activity of alkamides from Asteraceae, a dichloromethane extract from the roots of Anacyclus pyrethrum L. showed a moderate in vitro activity against the NF54 strain of Plasmodium falciparum and against Leishmania donovani (amastigotes, MHOM/ET/67/L82 strain). Seven pure alkamides and a mixture of two further alkamides were isolated by column chromatography followed by preparative high performance liquid chromatography. The alkamides were identified by mass- and NMR-spectroscopic methods as tetradeca-2E, 4E-dien-8,10-diynoic acid isobutylamide (anacycline, 1), deca-2E, 4E-dienoic acid isobutylamide (pellitorine, 2), deca-2E, 4E, 9-trienoic acid isobutylamide (3), deca-2E, 4E-dienoic acid 2-phenylethylamide (4), undeca-2E, 4E-dien-8,10-diynoic acid isopentylamide (5), tetradeca-2E, 4E, 12Z-trien-8,10-diynoic acid isobutylamide (6), and dodeca-2E, 4E-dien acid 4-hydroxy-2-phenylethylamide (7). Two compounds-undeca-2E, 4E-dien-8,10-diynoic acid 2-phenylethylamide (8) and deca-2E, 4E-dienoic acid 4-hydroxy-2-phenylethylamide (9)-were isolated as an inseparable mixture (1: 4). Compounds 3, 4, and 5 were isolated from Anacyclus pyrethrum L. for the first time. While compounds 4 and 5 were previously known from the genus Achillea, compound 3 is a new natural product, to the best of our knowledge. All isolated alkamides were tested in vitro for antiprotozoal activity against Plasmodium falciparum, Trypanosoma brucei rhodesiense, Trypanosoma cruzi, and Leishmania donovani and for cytotoxicity against L6 rat skeletal myoblasts.