Journal
MOLECULES
Volume 26, Issue 18, Pages -Publisher
MDPI
DOI: 10.3390/molecules26185675
Keywords
(+)-strebloside; cytotoxicity; Na+; K+-ATPase; docking profiles; molecular targets
Funding
- National Cancer Institute, National Institutes of Health [P01 CA125066]
Ask authors/readers for more resources
The study found that (+)-strebloside may be more promising than digoxin in developing potential anticancer agents, as it can target multiple molecular targets and mediate the antitumor activity of cardiac glycosides.
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-kappa B, 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available