N-substituted benzenesulfonamide compounds: DNA binding properties and molecular docking studies

Area of Science:

• Medicinal Chemistry
• Molecular Biology
• Biophysical Chemistry

Background:

• Benzenesulfonamide derivatives are explored for biological activities.
• Understanding DNA-ligand interactions is crucial for drug development.

Purpose of the Study:

• Synthesize and characterize novel benzenesulfonamide-based imine compounds.
• Investigate the binding properties of these compounds with FSdsDNA.
• Elucidate the binding mechanism using spectroscopic and computational methods.

Main Methods:

• Chemical synthesis of compounds 5-8.
• Spectroscopic and analytical characterization (e.g., NMR, Mass Spectrometry).
• DNA-binding studies using fluorescence spectroscopy (ethidium bromide displacement assay).
• Molecular docking simulations.

Main Results:

• Compounds 5-8 were successfully synthesized and characterized.
• Compound 8 exhibited the highest binding affinity to FSdsDNA (K_b = 3.10 × 10^4 M⁻¹).
• Compounds displaced ethidium bromide from DNA, indicating intercalation or groove binding.
• Molecular docking revealed binding within the minor groove via hydrogen bonds with DNA nucleotides.

Conclusions:

• Benzenesulfonamide-based imines show promise as DNA-binding agents.
• Compound 8 is a potential lead for further development in DNA-targeting therapies.
• The minor groove binding via hydrogen bonding is a key interaction mode.