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Interaction between antidepressant drug trazodone with double-stranded DNA: Multi-spectroscopic and computational
Ambrish Kumar1, Moumita Saha1, Juhi Saraswat2
1Centre of Advanced Studies, Department of Chemistry, Banaras Hindu University, Varanasi 221005, India.
International Journal of Biological Macromolecules
|July 24, 2024
Summary
Trazodone, an antidepressant, interacts with DNA primarily through minor groove binding, not electrostatic interactions. This understanding is crucial for developing safer antidepressant medications with fewer side effects.
Area of Science:
- Pharmacology
- Molecular Biology
- Biophysics
Background:
- Trazodone (TZD) is an antidepressant used for depression and sleep disorders.
- High doses can cause central nervous system depression with adverse effects.
- Understanding TZD's DNA interaction mechanism is key to developing safer drugs.
Purpose of the Study:
- To investigate the mode of interaction between trazodone and DNA.
- To elucidate the binding mechanism using spectroscopic and computational methods.
Main Methods:
- UV-vis titration and absorption spectroscopy.
- Steady-state fluorescence studies (Lehrer equation).
- DNA melting assays, dye displacement assays, circular dichroism (CD) spectroscopy.
- Molecular docking and molecular dynamics simulations.
- Ionic strength studies.
Main Results:
- UV-vis titration confirmed effective interaction between TZD and DNA.
- Stern-Volmer constant (KSV) calculated as 5.84 × 106 M-1.
- Spectroscopic and computational studies indicated TZD binds to DNA via the minor groove.
- Molecular dynamics confirmed a stable TZD-DNA complex with minor groove binding.
- Ionic strength studies revealed no significant electrostatic binding.
Conclusions:
- Trazodone binds to DNA within the minor groove.
- The interaction is not primarily electrostatic.
- This finding aids in designing Trazodone analogs with improved safety profiles.
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