ArticleScientific reports2016
Novel stereoselective bufadienolides reveal new insights into the requirements for Na(+), K(+)-ATPase inhibition by cardiotonic steroids.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 30 citations in OpenAlex.
- Cardiac Glycoside 3β-Bufalin Suppresses Cancer Cell Proliferation by Coupling with NaInternational journal of molecular sciences · 2026Article
- Chronic Administration of Marinobufagenin in Mice Causes Hyperlocomotion and Decrease in Anxiety by Altering Monoamine Turnover Unaccompanied by Motor Deficits or Oxidative Stress.International journal of molecular sciences · 2026Article
- Derivatization of Bufadienolides at Carbon-3 of the Steroid Core and Their Consequences for the Interaction with NaInternational journal of molecular sciences · 2025Article
- 3α-Hydroxybufadienolides in Bufo gallbladders: structural insights and biotransformation.Natural products and bioprospecting · 2024Article
- Current Targets and Future Directions of Positive Inotropes for Heart Failure.Current medicinal chemistry · 2024Review
- Identification of NaInternational journal of molecular sciences · 2023Article
- Tunable Toxicity of Bufadienolides is Regulated through a Configuration Inversion Catalyzed by a Short-Chain Dehydrogenase/Reductase.Chembiochem : a European journal of chemical biology · 2022Article
- Chemistry and the Potential Antiviral, Anticancer, and Anti-Inflammatory Activities of Cardiotonic Steroids Derived from Toads.Molecules (Basel, Switzerland) · 2022Review
- The impact of multiple climatic and geographic factors on the chemical defences of Asian toads (Bufo gargarizans Cantor).Scientific reports · 2019Article
- A Nonhospitable Host: Targeting Cellular Factors as an Antiviral Strategy for Respiratory Viruses.American journal of respiratory cell and molecular biology · 2018Article
- Probing the stereoselectivity of OleD-catalyzed glycosylation of cardiotonic steroids.RSC advances · 2018Article
- Mode of Action of the Natural Insecticide, Decaleside Involves Sodium Pump Inhibition.PloS one · 2017Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cardiotonic steroids (CTS) are clinically important drugs for the treatment of heart failure owing to their potent inhibition of cardiac Na(+), K(+)-ATPase (NKA). Bufadienolides constitute one of the two major classes of CTS, but little is known about how they interact with NKA. We report a remarkable stereoselectivity of NKA inhibition by native 3β-hydroxy bufalin over the 3α-isomer, yet replacing the 3β-hydroxy group with larger polar groups in the same configuration enhances inhibitory potency. Binding of the two (13)C-labelled glycosyl diastereomers to NKA were studied by solid-state NMR (SSNMR), which revealed interactions of the glucose group of the 3β- derivative with the inhibitory site, but much weaker interactions of the 3α- derivative with the enzyme. Molecular docking simulations suggest that the polar 3β-groups are closer to the hydrophilic amino acid residues in the entrance of the ligand-binding pocket than those with α-configuration. These first insights into the stereoselective inhibition of NKA by bufadienolides highlight the important role of the hydrophilic moieties at C3 for binding, and may explain why only 3β-hydroxylated bufadienolides are present as a toxic chemical defence in toad venom.
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