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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TL;DR: In this paper , the authors reported the isolation of five new (1-5) and eight known (7-13) cardiac glycosides (CGs) from the roots of Streblus asper Lour.
References
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Journal ArticleDOI
Anti-hepatitis B virus lignans from the root of Streblus asper.
TL;DR: Four new lignans were isolated from the ethyl acetate-soluble part of MeOH extract of the root of Streblus asper and evaluated for their anti-HBV activities in vitro using the HBV transfected HepG2.2.15 cell line.
Journal ArticleDOI
Peruvoside targets apoptosis and autophagy through MAPK Wnt/β-catenin and PI3K/AKT/mTOR signaling pathways in human cancers
TL;DR: The results demonstrated that Peruvoside has the ability to inhibit cancer cell proliferation by modulating the expression of various key proteins involved in cell cycle arrest, apoptosis, and autophagic cell death.
Journal ArticleDOI
The in vivo antitumor activity of cardiac glycosides in mice xenografted with human cancer cells is probably an experimental artifact.
TL;DR: The in vivo antitumor activity of cardiac glycosides in mice xenografted with human cancer cells is probably an experimental artifact.
Journal ArticleDOI
(+)-Strebloside-Induced Cytotoxicity in Ovarian Cancer Cells Is Mediated through Cardiac Glycoside Signaling Networks.
Wei Lun Chen,Yulin Ren,Jinhong Ren,Christian Erxleben,Michael E. Johnson,Saverio Gentile,A. Douglas Kinghorn,Steven M. Swanson,Steven M. Swanson,Joanna E. Burdette +9 more
TL;DR: In spite of its antitumor potential, the overall biological activity of (+)-strebloside must be regarded as being typical of better-known cardiac glycosides such as digoxin and ouabain.
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