Improving anti-trypanosomal activity of alkamides isolated from Achillea fragrantissima
Improving anti-trypanosomal activity of alkamides isolated from Achillea fragrantissima
Date
2017-11-03
Authors
Skaf, Joseph
Hamarsheh, Omar
Berninger, Michael
Balasubramanian, Srikkanth
Oelschlaeger, Tobias A.
Holzgrabe, Ulrike
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier B.V.
Abstract
In previous studies the aerial parts of Achillea fragrantissima were found to have substantial antileishmanial and
antitrypanosomal activity. A bioassay-guided fractionation of a dichloromethane extract yielded the isolation of
the essential anti-trypanosomal compounds of the plant. Seven sesquiterpene lactones (including Achillolide-A),
two flavonoids, chrysosplenol-D and chrysosplenetine, and four alkamides (including pellitorine) were identified.
This is the first report for the isolation of the sesquiterpene lactones 3 and 4, chrysosplenetine and the group
of alkamides from this plant. Bioevaluation against Trypanosoma brucei brucei TC221 (T.b brucei) using the
Alamar-Blue assay revealed the novel alkamide 13 to have an IC50 value of 40.37 μM. A compound library,
derived from the alkamide pellitorine (10), was synthesized and bioevaluated in order to find even more active
substances. The most active compounds 26 and 27 showed activities in submicromolar concentrations and selectivity
indices of 20.1 and 45.6, respectively, towards macrophage cell line J774.1. Toxicity of 26 and 27 was
assessed using the greater wax moth Galleria mellonella larvae as an in vivo model. No significant toxicity was
observed for the concentration range of 1.25–20 mM.
Description
Keywords
Achillea fragrantissima, Anti-trypanosomal, Sesquiterpene lactones, Flavonoids, Alkamides