TY - JOUR
T1 - Dioncophyllidine E
T2 - The first configurationally semi-stable, 7,3′-coupled naphthyldihydroisoquinoline alkaloid, from Ancistrocladus abbreviatus, with antiausterity activity against PANC-1 human pancreatic cancer cells
AU - Fayez, Shaimaa
AU - Cacciatore, Alessia
AU - Maneenet, Juthamart
AU - Nguyen, Hung Hong
AU - Tajuddeen, Nasir
AU - Feineis, Doris
AU - Assi, Laurent Aké
AU - Awale, Suresh
AU - Bringmann, Gerhard
N1 - Publisher Copyright:
© 2023 Elsevier Ltd
PY - 2023/4/15
Y1 - 2023/4/15
N2 - The discovery of a new naphthylisoquinoline alkaloid, dioncophyllidine E (4), from the tropical liana Ancistrocladus abbreviatus (Ancistrocladaceae) is described. Due to its rare 7,3′-coupling type, combined with the lack of an oxygen function at C-6, it is configurationally semi-stable at the biaryl axis, and thus occurs as a pair of slowly interconverting atropo-diastereomers, 4a and 4b. Its constitution was assigned mainly by 1D and 2D NMR. The absolute configuration at the stereocenter, C-3, was elucidated by oxidative degradation. The absolute axial configuration of the individual atropo-diastereomers was established by their HPLC resolution, combined with online electronic circular dichroism (ECD) investigations, providing nearly mirror-imaged LC-ECD spectra. These were assigned to the respective atropisomers by ECD comparison with a related, but configurationally stable alkaloid, ancistrocladidine (5). Dioncophyllidine E (4a/4b) exhibits a strong preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrient-deprived conditions, with a PC50 value of 7.4 µM, suggesting its potential as an agent against pancreatic cancer.
AB - The discovery of a new naphthylisoquinoline alkaloid, dioncophyllidine E (4), from the tropical liana Ancistrocladus abbreviatus (Ancistrocladaceae) is described. Due to its rare 7,3′-coupling type, combined with the lack of an oxygen function at C-6, it is configurationally semi-stable at the biaryl axis, and thus occurs as a pair of slowly interconverting atropo-diastereomers, 4a and 4b. Its constitution was assigned mainly by 1D and 2D NMR. The absolute configuration at the stereocenter, C-3, was elucidated by oxidative degradation. The absolute axial configuration of the individual atropo-diastereomers was established by their HPLC resolution, combined with online electronic circular dichroism (ECD) investigations, providing nearly mirror-imaged LC-ECD spectra. These were assigned to the respective atropisomers by ECD comparison with a related, but configurationally stable alkaloid, ancistrocladidine (5). Dioncophyllidine E (4a/4b) exhibits a strong preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrient-deprived conditions, with a PC50 value of 7.4 µM, suggesting its potential as an agent against pancreatic cancer.
KW - Ancistrocladus abbreviatus
KW - Antiausterity activity
KW - Dioncophyllidine E
KW - Naphthylisoquinoline alkaloids
KW - PANC-1 human pancreatic cancer cells
KW - Pancreatic cancer
UR - http://www.scopus.com/inward/record.url?scp=85150257349&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2023.129234
DO - 10.1016/j.bmcl.2023.129234
M3 - 学術論文
C2 - 36905967
AN - SCOPUS:85150257349
SN - 0960-894X
VL - 86
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
M1 - 129234
ER -
