Improving anti-trypanosomal activity of alkamides isolated from Achillea fragrantissima

dc.contributor.authorSkaf, Joseph
dc.contributor.authorHamarsheh, Omar
dc.contributor.authorBerninger, Michael
dc.contributor.authorBalasubramanian, Srikkanth
dc.contributor.authorOelschlaeger, Tobias A.
dc.contributor.authorHolzgrabe, Ulrike
dc.description.abstractIn 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.en_US
dc.description.sponsorshipWe thank Dr. Ulrich Hildebrandt and Dr. Gerd Vogg, Botanical garden, University of Würzburg, for identifying the seeds and plants of A. fragrantissima. We are grateful to Prof. Dr. August Stich, Medical Mission Institute, University of Würzburg, for providing the respective lab facilities to perform the anti-trypanosomal assay. Many thanks for Dr. Ludwig Hoellein for proof-reading the manuscript. We wish to thank the German Academic Exchange Service (DAAD) for the doctoral scholarship of Joseph Skaf (grant number: 57169181). Srikkanth Balasubramanian was supported by a grant of the German Excellence Initiative to the Graduate School of Life Sciences, University of Würzburg.en_US
dc.publisherElsevier B.V.en_US
dc.subjectAchillea fragrantissimaen_US
dc.subjectSesquiterpene lactonesen_US
dc.titleImproving anti-trypanosomal activity of alkamides isolated from Achillea fragrantissimaen_US
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