University of Würzburg, Institut für Pharmazie und Lebensmittelchemie, Am Hubland, 97074 Würzburg, Germany.
Al-Quds University, Faculty of Science & Technology, Department of Biology, P.O. Box 51000, Jerusalem, Palestine.
Fitoterapia. 2018 Mar;125:191-198. doi: 10.1016/j.fitote.2017.11.001. Epub 2017 Nov 3.
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 IC value of 40.37μM. 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 1.25-20mM.
在之前的研究中，发现香艾菊的地上部分具有很强的抗利什曼原虫和抗锥虫活性。一种二氯甲烷提取物的生物测定指导分离得到了该植物的主要抗锥虫化合物。分离得到了七种倍半萜内酯（包括 Achillolide-A）、两种黄酮类化合物、chrysosplenol-D 和 chrysosplenetine 以及四种酰胺（包括 pellitorine）。这是首次从这种植物中分离出倍半萜内酯 3 和 4、chrysosplenetine 和酰胺类化合物。用 Alamar-Blue 测定法对 Trypanosoma brucei brucei TC221（T.b brucei）进行生物评价，结果表明新型酰胺 13 的 IC 值为 40.37μM。为了寻找更有效的物质，从酰胺类化合物 pellitorine（10）衍生出了一个化合物库，并对其进行了生物评价。最具活性的化合物 26 和 27 在亚微摩尔浓度下表现出活性，对巨噬细胞系 J774.1 的选择性指数分别为 20.1 和 45.6。使用大蜡螟幼虫作为体内模型评估了 26 和 27 的毒性。在 1.25-20mM 的浓度范围内没有观察到显著的毒性。
