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6'-Fluoro-3-deazaneplanocin: Synthesis and antiviral properties, including Ebola
Chong Liu1, Qi Chen2, Steven Cardinale3
1Molette Laboratory for Drug Discovery, Department of Chemistry and Biochemistry, Auburn University, Auburn, AL 36849-5312, United States.
Bioorganic & Medicinal Chemistry Letters
|November 3, 2018
Summary
A novel synthesis of 6'-fluoro-3-deazaneplanocin was achieved, yielding a compound with potent anti-Ebola virus activity. This antiviral agent also showed efficacy against measles and H1N1, with low cytotoxicity.
Area of Science:
- Organic Chemistry
- Medicinal Chemistry
- Virology
Background:
- 3-Deazaneplanocin analogs are investigated for antiviral properties.
- Ebola virus remains a significant global health threat requiring novel therapeutic strategies.
- Structure-activity relationships of nucleoside analogs are crucial for drug development.
Purpose of the Study:
- To develop a stereospecific synthesis of 6 '-fluoro-3-deazaneplanocin.
- To evaluate the antiviral activity of the synthesized compound against Ebola virus and other viruses.
- To assess the compound's cytotoxicity and mechanism of action.
Main Methods:
- Stereospecific synthesis starting from d-ribose.
- Antiviral assays against Ebola (Zaire, Vero) and other viruses (measles, H1N1, Pichinde).
- Cytotoxicity assays (CC50) and selectivity index (SI) determination.
- Enzyme inhibition assays for S-adenosylhomocysteine hydrolase.
Main Results:
- A 15-step synthesis of 6 '-fluoro-3-deazaneplanocin was successfully completed.
- The compound exhibited significant activity against Ebola virus (EC50 < 0.36 μM) with a high selectivity index (>347).
- Moderate inhibition of S-adenosylhomocysteine hydrolase was observed, not directly correlating with anti-Ebola effects.
- Activity was also noted against measles, H1N1, and Pichinde viruses with limited cytotoxicity.
Conclusions:
- 6 '-fluoro-3-deazaneplanocin is a promising antiviral candidate with potent activity against Ebola virus.
- The compound's broad-spectrum activity warrants further investigation for therapeutic potential.
- The synthesis provides a viable route for producing this potentially valuable antiviral agent.