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Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
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Digitoxin analogues with improved anticytomegalovirus activity
Hongyi Cai1, Hua-Yu L Wang2, Rajkumar Venkatadri1
1Department of Pediatrics, Johns Hopkins University School of Medicine , Baltimore, Maryland 21287, United States.
ACS Medicinal Chemistry Letters
|June 6, 2014
Summary
Cardiac glycosides show promise as antiviral treatments. Digitoxin analogues were studied, revealing that specific sugar structures enhance their activity against cytomegalovirus (CMV).
Area of Science:
- Pharmacology
- Virology
- Organic Chemistry
Background:
- Cardiac glycosides are known for their potent anticancer and antiviral properties.
- Cytomegalovirus (CMV) is a significant opportunistic pathogen, particularly in immunocompromised individuals.
Purpose of the Study:
- To evaluate the anti-cytomegalovirus (CMV) activity of digitoxin and its analogues.
- To explore the structure-activity relationship (SAR) of cardiac glycosides against CMV.
Main Methods:
- Synthesis and testing of digitoxin analogues with varying sugar moieties.
- In vitro evaluation of antiviral activity against CMV.
- Structure-activity relationship (SAR) analysis.
Main Results:
- Cardiac glycosides exhibit antiviral activity against CMV at nanomolar concentrations.
- The type and length of the sugar moiety attached to the steroid core significantly influence anti-CMV activity.
- Cardiac glycosides containing l-sugars demonstrated enhanced anti-CMV efficacy.
Conclusions:
- Specific structural modifications, particularly the inclusion of l-sugars, can improve the anti-CMV activity of cardiac glycosides.
- These findings contribute to understanding the mechanism of CMV inhibition by cardiac glycosides.
- Cardiac glycosides represent a potential therapeutic avenue for CMV infections.
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