Groove binding mediated structural modulation and DNA cleavage by quinoline appended chalcone derivative

Area of Science:

• Biochemistry
• Molecular Biology
• Medicinal Chemistry

Background:

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

Purpose of the Study:

• To investigate the DNA binding interaction of a novel quinoline appended chalcone derivative, ADMQ.
• To elucidate the binding mode and consequences of ADMQ-DNA interaction.

Main Methods:

• UV-Vis absorption spectroscopy
• Steady-state fluorescence spectroscopy
• Fluorescence anisotropy
• Circular dichroism
• Helix melting studies
• Agarose gel electrophoresis
• Molecular docking
• Induced Fit Docking (IFD)
• Molecular dynamics (MD) simulation

Main Results:

• ADMQ interacts with calf thymus DNA (ctDNA) via non-covalent minor groove binding.
• Spectroscopic and biophysical methods confirmed groove binding.
• Molecular simulations showed ADMQ induces DNA unwinding, bending, and backbone rigidification.
• ADMQ causes concentration-dependent cleavage of plasmid DNA.

Conclusions:

• ADMQ exhibits significant DNA binding affinity and induces structural alterations.
• The findings provide insights into heterocyclic chalcone-DNA interactions.
• ADMQ shows potential as a basis for future therapeutic agents targeting nucleic acids.