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Published on: March 3, 2023
Probing DNA damage induced by common antiviral agents using multiple analytical techniques
Amira F El-Yazbi1, Glen R Loppnow2
1Department of Chemistry, University of Alberta, Edmonton, AB T6G 2G2, Canada; Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
Certain antiviral drugs, daclatasvir and ledipasvir, can damage DNA, potentially offering new treatments for hepatocellular carcinoma (liver cancer) in patients resistant to standard therapies.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Hepatocellular carcinoma (HCC) is a prevalent global malignancy.
- Chronic hepatitis B and C infections are primary causes of HCC worldwide.
- Investigating novel therapeutic strategies for HCC is crucial, especially for drug-resistant cases.
Purpose of the Study:
- To explore the DNA damaging effects of FDA-approved antiviral drugs.
- To elucidate the mechanism of action of potential anticancer agents for HCC.
- To identify antiviral drugs that may serve as alternative treatments for HCC.
Main Methods:
- Absorption spectroscopy to detect DNA structural changes.
- MALDI-TOF mass spectrometry to identify DNA strand breaks.
- Fluorimetric analysis using EvaGreen dye to assess drug-DNA interactions.
Main Results:
- Daclatasvir and ledipasvir were found to induce DNA damage.
- Spectroscopic and mass spectrometry data indicated disruption of DNA structure and strand breaks.
- EvaGreen fluorescence reduction suggested drug-induced DNA damage, particularly in guanine-rich regions.
Conclusions:
- Daclatasvir and ledipasvir exhibit DNA damaging properties, likely via oxidative mechanisms.
- These antiviral drugs show promise as alternative treatments for drug-resistant HCC.
- Drug concentration and guanine-rich DNA regions influence the observed DNA damage.
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