TY - JOUR
T1 - Ealamines A-H, a Series of Naphthylisoquinolines with the Rare 7,8′-Coupling Site, from the Congolese Liana Ancistrocladus ealaensis, Targeting Pancreatic Cancer Cells
AU - Tshitenge, Dieudonné Tshitenge
AU - Bruhn, Torsten
AU - Feineis, Doris
AU - Schmidt, David
AU - Mudogo, Virima
AU - Kaiser, Marcel
AU - Brun, Reto
AU - Würthner, Frank
AU - Awale, Suresh
AU - Bringmann, Gerhard
N1 - Publisher Copyright:
© 2019 American Chemical Society and American Society of Pharmacognosy.
PY - 2019/11/22
Y1 - 2019/11/22
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85073832829&partnerID=8YFLogxK
U2 - 10.1021/acs.jnatprod.9b00755
DO - 10.1021/acs.jnatprod.9b00755
M3 - 学術論文
C2 - 31630523
AN - SCOPUS:85073832829
SN - 0163-3864
VL - 82
SP - 3150
EP - 3164
JO - Journal of Natural Products
JF - Journal of Natural Products
IS - 11
ER -