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Dissecting Host-virus Interaction in Lytic Replication of a Model Herpesvirus
Published on: October 7, 2011
Interaction of calf thymus DNA with the antiviral drug Lamivudine
Nahid Shahabadi1, Maryam Maghsudi, Maryam Mahdavi
1Department of Inorganic Chemistry, Faculty of Chemistry, Razi University, Kermanshah, Iran. nahidshahabadi@yahoo.com
Abstract:
One approach to accelerate the availability of new cancer drugs is to test drugs approved for other conditions as anticancer agents. In recent years, some researchers have shown that antiviral drugs, such as ritonavir, saquinavir, and nelfinavir, inhibit the growth of over 60 cancer cell lines derived from nine different tumor types. This article studied the anticancer potential of an antiviral drug, lamivudine (LA). The interaction of LA and calf thymus DNA (CT-DNA) was studied using emission, absorption, circular dichroism (CD), and viscosity techniques. The binding constants evaluated from fluorescence data at different temperatures revealed that fluorescence enhancement is a static process that involves complex-DNA formation in the ground state. Further, the enthalpy and entropy of the reaction between the drug and CT-DNA showed ΔH<0 (-126.38±0.61 kJ mol(-1)) and ΔS<0 (-352.17±2.1 J mol(-1) K(-1)); therefore, van der Waals interactions or hydrogen bonds are the main forces in the binding of LA to CT-DNA. The values of K(f) clearly underscore the high affinity of LA to DNA. In addition, detectable changes in the CD spectrum of CT-DNA in the presence of LA indicated conformational changes. All these results showed that groove binding is the binding mode of this drug and CT-DNA.
Insights
Antiviral drug lamivudine (LA) shows anticancer potential by interacting with calf thymus DNA (CT-DNA). This study reveals LA binds to DNA via groove binding, suggesting a new therapeutic avenue for cancer treatment.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Drug repurposing accelerates the development of new cancer therapies.
- Antiviral drugs like ritonavir have demonstrated efficacy against various cancer cell lines.
- Lamivudine (LA), an antiviral medication, is investigated for its anticancer properties.
Purpose of the Study:
- To investigate the anticancer potential of lamivudine (LA).
- To elucidate the interaction mechanism between LA and calf thymus DNA (CT-DNA).
Main Methods:
- Spectroscopic techniques including emission and absorption spectroscopy.
- Circular dichroism (CD) and viscosity measurements.
- Thermodynamic analysis of drug-DNA binding.
Main Results:
- Fluorescence data indicate a static binding process with complex-DNA formation.
- Thermodynamic parameters (ΔH<0, ΔS<0) suggest van der Waals forces or hydrogen bonds mediate LA-DNA binding.
- CD spectral changes and viscosity data confirm groove binding of LA to CT-DNA.
Conclusions:
- Lamivudine (LA) exhibits significant affinity for calf thymus DNA (CT-DNA).
- The binding mechanism involves groove binding, indicating potential anticancer activity.
- LA's interaction with DNA supports its investigation as a novel cancer therapeutic agent.
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