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Interaction of (+)-Strebloside and Its Derivatives with Na+/K+-ATPase and Other Targets.

Yulin RenSijin WuSijie ChenJoanna E BurdetteXiaolin ChengAlan Douglas Kinghorn
Published in: Molecules (Basel, Switzerland) (2021)
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.
Keyphrases
  • oxidative stress
  • signaling pathway
  • protein protein
  • left ventricular
  • cell proliferation
  • endothelial cells
  • endoplasmic reticulum
  • nuclear factor
  • pi k akt
  • atomic force microscopy
  • binding protein
  • dna binding