Alprazolam Intercalates into DNA

In vitro interaction of a benzodiazepine group of drugs Alprazolam (Alp), a hypnotic and tranquilizer, with DNA was studied by various methods. Absorption spectrophotometric study showed that Alp binds strongly with supercoiled pUC 19 DNA and the calculated binding constant is 8.245 × 10 3 M −1 in 1...

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Bibliographic Details
Published in:Journal of biomolecular structure & dynamics 2009-02, Vol.26 (4), p.421-429
Main Authors: Saha, Biswarup, Mukherjee, Ananda, Santra, Chitta Ranjan, Chattopadhyay, Atiskumar, Ghosh, Amar Nath, Choudhuri, Utpal, Karmakar, Parimal
Format: Article
Language:English
Subjects:
Alprazolam
Alprazolam - chemistry
Circular Dichroism
DNA
DNA - chemistry
Ethidium - chemistry
Gel electrophoresis
Hypnotics and Sedatives - chemistry
Intercalating Agents - chemistry
Intercalation
Microscopy, Electron, Transmission
Nucleic Acid Conformation
Plasmids - chemistry
Plasmids - ultrastructure
Spectrometry, Fluorescence
Spectroscopic study
Transition Temperature
Transmission electron microscopy
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Summary:In vitro interaction of a benzodiazepine group of drugs Alprazolam (Alp), a hypnotic and tranquilizer, with DNA was studied by various methods. Absorption spectrophotometric study showed that Alp binds strongly with supercoiled pUC 19 DNA and the calculated binding constant is 8.245 × 10 3 M −1 in 10 mM Tris-Cl buffer, pH 7.4. Spectrofluorometric study showed that ethidium bromide induced DNA fluorescence intensity was reduced completely after addition of Alp. But Alp did not interfere with the interaction of Hoechst 33258, a DNA minor groove binder, with plasmid DNA. Circular dichroic spectroscopic study showed that with the gradual increase in Alp concentrations, both the positive and the negative peaks of DNA were gradually decreased and at higher concentrations of Alp (60 μM and 80 μM), the negative peaks became positive indicating the intercalation and the conformational change in the DNA. Binding of Alp with DNA increased the thermal stability of DNA by 6 °C with respect to the mock treated sample. Gel electrophoresis study of supercoiled pUC 19 DNA showed more compact structure as a result of Alp binding. Transmission electron microscopic observations also confirmed this compactness. Thus, our observations suggest the strong interaction of Alp with DNA, which may raise serious questions about the random uses of Alprazolam.
ISSN:0739-1102
1538-0254
DOI:10.1080/07391102.2009.10507257