Hydroxychloroquine Exhibits a Strong Complex Interaction with DNA: Unraveling the Mechanism of Action

In the past months, the use of the drug hydroxychloroquine has considerably increased in many countries, associated with a proposed treatment for the COVID-19 disease. Although there is no conclusive evidence about the efficacy of the drug for this purpose, surprisingly there are no conclusive studi...

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Bibliographic Details
Published in:The journal of physical chemistry letters 2020-11, Vol.11 (22), p.9528-9534
Main Authors: Bazoni, R. F, Moura, T. A, Rocha, M. S
Format: Article
Language:English
Subjects:
DNA - chemistry
Electrophoresis
Hydroxychloroquine - chemistry
Intercalating Agents - chemistry
Optical Tweezers
Physical Insights into Materials and Molecular Properties
Single Molecule Imaging
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Summary:In the past months, the use of the drug hydroxychloroquine has considerably increased in many countries, associated with a proposed treatment for the COVID-19 disease. Although there is no conclusive evidence about the efficacy of the drug for this purpose, surprisingly there are no conclusive studies in the literature concerning its mechanism of action inside cells, which is related to its interaction with nucleic acids. Here, we performed a robust characterization of the interaction between hydroxychloroquine and double-stranded DNA using single-molecule force spectroscopy and gel electrophoresis. Two different binding modes were identified, namely, minor groove binding for low drug concentrations and intercalation for high drug concentrations, and the sets of binding parameters were determined for each of these modes. Such results have unraveled in detail the molecular mechanism of action of the drug as a DNA ligand.
ISSN:1948-7185
1948-7185
DOI:10.1021/acs.jpclett.0c02590