Structures, chemotaxonomic significance, cytotoxic and Na+, K+-ATPase inhibitory activities of new cardenolides from Asclepias curassavica

Zhang, Rong-Rong and Tian, Hai-Yan and Tan, Ya-Fang and Chung, Tse-Yu and Sun, Xiao-Hui and Xia, Xue and Ye, Wen-Cai and Middleton, David A. and Fedosova, Natalya and Esmann, Mikael and Tzen, Jason T. C. and Jiang, Ren-Wang (2014) Structures, chemotaxonomic significance, cytotoxic and Na+, K+-ATPase inhibitory activities of new cardenolides from Asclepias curassavica. Organic and Biomolecular Chemistry, 12 (44). pp. 8919-8929. ISSN 1477-0520

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Abstract

Five new cardenolide lactates (1-5) and one new dioxane double linked cardenolide glycoside (17) along with 15 known compounds (6-16 and 18-21) were isolated from the ornamental milkweed Asclepias curassavica. Their structures were elucidated by extensive spectroscopic methods (IR, UV, MS, 1D- and 2D-NMR). The molecular structures and absolute configurations of 1-3 and 17 were further confirmed by single-crystal X-ray diffraction analysis. Simultaneous isolation of dioxane double linked cardenolide glycosides (17-21) and cardenolide lactates (1-5) provided unique chemotaxonomic markers for this genus. Compounds 1-21 were evaluated for the inhibitory activities against DU145 prostate cancer cells. The dioxane double linked cardenolide glycosides showed the most potent cytotoxic effect followed by normal cardenolides and cardenolide lactates, while the C21 steroids were non-cytotoxic. Enzymatic assay established a correlation between the cytotoxic effects in DU145 cancer cells and the K-i for the inhibition of Na+, K+-ATPase. Molecular docking analysis revealed relatively strong H-bond interactions between the bottom of the binding cavity and compounds 18 or 20, and explained why the dioxane double linked cardenolide glycosides possessed higher inhibitory potency on Na+, K+-ATPase than the cardenolide lactate.

Item Type:
Journal Article
Journal or Publication Title:
Organic and Biomolecular Chemistry
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/1600/1606
Subjects:
ID Code:
72097
Deposited By:
Deposited On:
10 Dec 2014 08:56
Refereed?:
Yes
Published?:
Published
Last Modified:
29 Oct 2020 03:46