Determination of the cationic amphiphilic drug–DNA binding mode and DNA-assisted fluorescence resonance energy transfer amplification

• Comparative study of cationic amphiphilic drugs (CADs) with DNA.
• CD results suggest structural alterations of DNA in presence of CADs.
• Ethidium bromide (EB) and other techniques support intercalative mode of binding.
• Fluorescence exchange energy transfer in between CADs and EB using DNA as a template.

Understanding the mechanism of drug–DNA binding is crucial for predicting the potential genotoxicity of drugs. Agarose gel electrophoresis, absorption, steady state fluorescence, and circular dichroism have been used in exploring the interaction of cationic amphiphilic drugs (CADs) such as amitriptyline hydrochloride (AMT), imipramine hydrochloride (IMP), and promethazine hydrochloride (PMT) with calf thymus or pUC19 DNA. Agarose gel electrophoresis assay, along with absorption and steady state fluorescence studies, reveal interaction between the CADs and DNA. A comparative study of the drugs with respect to the effect of urea, iodide induced quenching, and ethidium bromide (EB) exclusion assay reflects binding of CADs to the DNA primarily in an intercalative fashion. Circular dichroism data also support the intercalative mode of binding. Besides quenching, there is fluorescence exchange energy transfer (FRET) in between CADs and EB using DNA as a template.

Energy exchanges between ethidium bromide and cationic amphiphilic drug using DNA as a template.Figure optionsDownload as PowerPoint slide