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-2 E ,4 E -dienoic acid isobutylamide (pellitorine, 2 ), deca-2 E ,4 E ,9-trienoic acid isobutylamide ( 3 ), deca-2 E ,4 E -dienoic acid 2-phenylethylamide ( 4 ), undeca-2 E ,4 E -dien-8,10-diynoic acid isopentylamide ( 5 ), tetradeca-2 E ,4 E ,12 Z -trien-8,10-diynoic acid isobutylamide ( 6 ), and dodeca-2 E ,4 E -dien acid 4-hydroxy-2-phenylethylamide ( 7 ). Two compounds-undeca-2 E ,4 E -dien-8,10-diynoic acid 2-phenylethylamide ( 8 ) and deca-2 E ,4 E -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.