Interaction between antidepressant drug trazodone with double-stranded DNA: Multi-spectroscopic and computational analysis

Abstract

Trazodone (TZD) is an antidepressant drug used to treat major depressive and sleeping disorders. Elevated doses of trazodone are associated with central nervous system depression, which manifests as nausea, drowsiness, confusion, vertigo, exhaustion, etc. To develop a clinically viable active pharmaceutical compound with minimal adverse effects, it is imperative to possess a comprehensive knowledge of the drug's action mechanism on DNA. Hence, we investigate the mode of interaction between trazodone and DNA utilizing various spectroscopic and computational techniques. Studies using UV–vis titration showed that the DNA and trazodone have an effective interaction. The magnitude of the Stern-Volmer constant (KSV) has been calculated to be 5.84 × 106 M−1 by the Lehrer equation from a steady-state fluorescence study. UV–vis absorption, DNA melting, dye displacement, and circular dichroism studies suggested that trazodone binds with DNA in minor grooves. Molecular docking and molecular dynamic simulation demonstrated that the TZD-DNA system was stable, and the mode of binding was minor groove. Furthermore, ionic strength investigation demonstrates that DNA and trazodone do not have a substantial electrostatic binding interaction. © 2024 Elsevier B.V.