Interaction of (+)-Strebloside and Its Derivatives with Na +/K +-ATPase and Other Targets
TLDR
In this article, the docking profiles for (+)-strebloside, a cytotoxic cardiac glycoside identified from Streblus asper, and some of its derivatives and Na+/K+-ATPase have been investigated.Abstract:
Docking profiles for (+)-strebloside, a cytotoxic cardiac glycoside identified from Streblus asper, and some of its derivatives and Na+/K+-ATPase have been investigated. In addition, binding between (+)-strebloside and its aglycone, strophanthidin, and several of their other molecular targets, including FIH-1, HDAC, KEAP1 and MDM2 (negative regulators of Nrf2 and p53, respectively), NF-κB, and PI3K and Akt1, have been inspected and compared with those for digoxin and its aglycone, digoxigenin. The results showed that (+)-strebloside, digoxin, and their aglycones bind to KEAP1 and MDM2, while (+)-strebloside, strophanthidin, and digoxigenin dock to the active pocket of PI3K, and (+)-strebloside and digoxin interact with FIH-1. Thus, these cardiac glycosides could directly target HIF-1, Nrf2, and p53 protein-protein interactions, Na+/K+-ATPase, and PI3K to mediate their antitumor activity. Overall, (+)-strebloside seems more promising than digoxin for the development of potential anticancer agents.read more
Citations
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Cardiac glycosides from the roots of Streblus asper Lour. with activity against Epstein-Barr virus lytic replication.
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References
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Journal ArticleDOI
Structural Insights into the Interactions of Digoxin and Na+/K+-ATPase and Other Targets for the Inhibition of Cancer Cell Proliferation
TL;DR: In this paper, the docking profiles for digoxin and several derivatives and Na+/K+-ATPase were investigated; an additional small Asn130 side pocket was revealed, which could be useful in the design of novel digoxin-like antitumor agents.
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Cardiac glycosides from the roots of Streblus asper Lour. and their apoptosis-inducing activities in A549 cells
Bo-dou Zhang,Wanfang Zhu,Toshihiro Akihisa,Takashi Kikuchi,Motohiko Ukiya,Fukuda Maya,Jian Xu,Wenyuan Liu,Feng Feng,Jie Zhang +9 more
TL;DR: The effects of the cardiac glycosides on apoptosis and cytotoxicity were examined in human A549 lung cancer cells and all the compounds showed remarkable inhibitory activities, with IC50 values in the range of 0.01-6.08 μM.
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