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Single-Molecule Fluorescence Visualization of DNA Polymerase Dynamics at G-Quadruplexes
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A new class of quadruplex DNA-binding nickel Schiff base complexes
Son Q T Pham1, Nawal Assadawi1, Jadon Wells1
1School of Chemistry and Molecular Bioscience, University of Wollongong, Northfields Avenue, Wollongong 2522, Australia. sralph@uow.edu.au and Molecular Horizons, University of Wollongong, Northfields Avenue, Wollongong 2522, Australia.
Dalton Transactions (Cambridge, England : 2003)
|March 29, 2020
Summary
New nickel Schiff base complexes show selective binding to quadruplex DNA (qDNA) over double-stranded DNA (dsDNA). Complex 14 demonstrates significant potential for qDNA interactions and exhibits promising anti-cancer activity against lung cancer cells.
Area of Science:
- Coordination Chemistry
- Bioinorganic Chemistry
- Medicinal Chemistry
Background:
- Nickel(II) Schiff base complexes are explored for their biological activities.
- DNA-binding agents are crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To synthesize and characterize novel nickel(II) Schiff base complexes with pendant ethylpiperidine groups.
- To investigate the DNA binding properties of these complexes, focusing on quadruplex DNA (qDNA) and double-stranded DNA (dsDNA).
- To evaluate the potential anti-cancer activity of the synthesized complexes.
Main Methods:
- Synthesis of nickel(II) Schiff base complexes.
- Electrospray Ionization Mass Spectrometry (ESI-MS) for non-covalent complex detection.
- Circular Dichroism (CD) spectroscopy to study DNA structural changes.
- Fluorescent Indicator Displacement (FID) and Förster Resonance Energy Transfer (FRET) assays for DNA binding affinity.
- Cytotoxicity assays using Chinese hamster lung cancer (V79) cells.
Main Results:
- Six new nickel(II) Schiff base complexes with ethylpiperidine moieties were synthesized, exhibiting enhanced water solubility.
- Complex 14 selectively formed non-covalent complexes with parallel tetramolecular quadruplex DNA (Q4) and unimolecular quadruplex DNA (qDNA), but not with double-stranded DNA (dsDNA).
- CD, FID, and FRET assays confirmed strong binding affinity of complex 14 to qDNA structures.
- Cytotoxicity studies revealed IC50 values between 4-12 μM for complex 14 against V79 lung cancer cells, with induction of apoptosis.
Conclusions:
- The synthesized nickel(II) Schiff base complex 14 exhibits selective binding to quadruplex DNA structures.
- Complex 14 shows significant potential as a lead compound for developing novel DNA-targeting agents.
- The observed cytotoxicity and apoptosis induction highlight the therapeutic potential of these nickel complexes in cancer treatment.
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