Selective (α)-l-Rhamnosylation and Neuroprotective Activity Exploration of Cardiotonic Steroids.

Journal article

Ryan Rutkoski, L. Debarba, L. Stilgenbauer, Tay Rosenthal, M. Sadagurski, P. Nagorny
ACS Medicinal Chemistry Letters, 2024

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APA Click to copy
Rutkoski, R., Debarba, L., Stilgenbauer, L., Rosenthal, T., Sadagurski, M., & Nagorny, P. (2024). Selective (α)-l-Rhamnosylation and Neuroprotective Activity Exploration of Cardiotonic Steroids. ACS Medicinal Chemistry Letters.

Chicago/Turabian Click to copy
Rutkoski, Ryan, L. Debarba, L. Stilgenbauer, Tay Rosenthal, M. Sadagurski, and P. Nagorny. “Selective (α)-l-Rhamnosylation and Neuroprotective Activity Exploration of Cardiotonic Steroids.” ACS Medicinal Chemistry Letters (2024).

MLA Click to copy
Rutkoski, Ryan, et al. “Selective (α)-l-Rhamnosylation and Neuroprotective Activity Exploration of Cardiotonic Steroids.” ACS Medicinal Chemistry Letters, 2024.

BibTeX Click to copy

@article{ryan2024a,
  title = {Selective (α)-l-Rhamnosylation and Neuroprotective Activity Exploration of Cardiotonic Steroids.},
  year = {2024},
  journal = {ACS Medicinal Chemistry Letters},
  author = {Rutkoski, Ryan and Debarba, L. and Stilgenbauer, L. and Rosenthal, Tay and Sadagurski, M. and Nagorny, P.}
}

Abstract

This work describes the studies on the direct C3-glycosylation of the C19-hydroxylated cardiotonic steroids strophanthidol, anhydro-ouabagenin, and ouabagenin using a strategy based on in situ protection of the C5 and C19 hydroxyl groups with boronic acids. While this strategy resulted in a successful one-pot C3-selective glycosylation of strophanthidol and anhydro-ouabegenin, it failed to provide ouabain from ouabagenin. The neuroprotective activity of the synthetic and natural glycosides against LPS-induced neuroinflammation was explored in neonatal mouse primary glia cells. Co-administration of natural and synthetic C3-glycosides at 200 nM concentrations resulted in the significant reduction of the LPS-induced neuroinflammatory markers IL-6, IL-1, TNFα, and IKBKE, with the anhydro-ouabagenin-3-(α)-l-rhamnoside (anhydro-ouabain) showing the most significant effect. At the same time, unglycosylated anhydro-ouabagenin enhanced rather than suppressed LPS-induced neuroinflammation.