Ealamines A-H, a Series of Naphthylisoquinolines with the Rare 7,8′-Coupling Site, from the Congolese Liana Ancistrocladus ealaensis, Targeting Pancreatic Cancer Cells

Dieudonné Tshitenge Tshitenge, Torsten Bruhn, Doris Feineis, David Schmidt, Virima Mudogo, Marcel Kaiser, Reto Brun, Frank Würthner, Suresh Awale, Gerhard Bringmann*

*この論文の責任著者

研究成果: ジャーナルへの寄稿学術論文査読

20 被引用数 (Scopus)

抄録

From the twigs and leaves of the Central African liana Ancistrocladus ealaensis (Ancistrocladaceae), a series of ten 7,8′-coupled naphthylisoquinoline alkaloids were isolated, comprising eight new compounds, named ealamines A-H (4a, 4b, 5-10), and two known ones, 6-O-demethylancistrobrevine A (11) and yaoundamine A (12), which had previously been found in related African Ancistrocladus species. Only one of the new compounds within this series, ealamine H (10), is a typical Ancistrocladaceae-type alkaloid, with 3S-configuration at C-3 and an oxygen function at C-6, whereas seven of the new alkaloids are the first 7,8′-linked "hybrid-type" naphthylisoquinoline alkaloids, i.e., 3R-configured and 6-oxygenated in the tetrahydroisoquinoline part. The discovery of such a broad series of 7,8′-coupled naphthyltetrahydroisoquinolines is unprecedented, because representatives of this subclass of alkaloids are normally found in Nature quite rarely. The stereostructures of the new ealamines were assigned by HRESIMS, 1D and 2D NMR, oxidative degradation, and experimental and quantum-chemical ECD investigations, and - in the case of ealamine A (4a) - also confirmed by X-ray diffraction analysis. Ealamines A-D exhibited distinct - and specific - antiplasmodial activities, and they displayed pronounced preferential cytotoxic effects toward PANC-1 human pancreatic cancer cells in nutrient-deprived medium, without causing toxicity under normal, nutrient-rich conditions, with ealamine C (5) as the most potent agent.

本文言語英語
ページ(範囲)3150-3164
ページ数15
ジャーナルJournal of Natural Products
82
11
DOI
出版ステータス出版済み - 2019/11/22

ASJC Scopus 主題領域

  • 分析化学
  • 分子医療
  • 薬理学
  • 薬科学
  • 創薬
  • 補完代替医療
  • 有機化学

フィンガープリント

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