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Exploring the interaction between a fluorescent Ag(I)-biscarbene complex and non-canonical DNA structures: a
Francesca Binacchi1, Ester Giorgi1, Giacomo Salvadori1
1Department of Chemistry and Industrial Chemistry, University of Pisa, Via G. Moruzzi 13, 56124 Pisa, Italy. francesca.binacchi@dcci.unipi.it.
Dalton Transactions (Cambridge, England : 2003)
|May 22, 2024
Summary
This study introduces a novel silver-biscarbene compound that targets G-quadruplex and i-motif DNA structures. This compound exhibits potent anticancer activity, outperforming cisplatin in ovarian cancer models.
Area of Science:
- Medicinal Chemistry
- Biochemistry
- Nanotechnology
Background:
- Silver compounds are recognized for antimicrobial properties and emerging anticancer potential.
- Non-canonical DNA structures like G-quadruplexes (G4) and i-motifs are crucial in cancer biology.
- Targeting these DNA structures offers a novel strategy for cancer therapy.
Purpose of the Study:
- To investigate a new Ag(I)-biscarbene complex for its ability to bind non-canonical DNA structures.
- To compare the DNA-binding and anticancer properties of the Ag(I) complex with its Au(I) counterpart.
- To evaluate the potential of these complexes as anticancer agents, particularly against cisplatin-resistant cancers.
Main Methods:
- Synthesis and characterization of Ag(I)-biscarbene and Au(I) complexes.
- DNA-binding studies using various non-canonical DNA structures (G4, i-motif).
- In silico studies to elucidate binding modes.
- Cytotoxicity assays against cancer cell lines, including cisplatin-resistant ovarian cancer.
- Binding studies with other biomolecules like RNA and proteins (BSA).
Main Results:
- The Ag(I)-biscarbene complex selectively binds to G-quadruplexes and i-motif DNA structures with distinct binding signatures.
- The Au(I) counterpart stabilizes mitochondrial G4 structures.
- Both complexes demonstrate enhanced cytotoxic activity compared to cisplatin, overcoming resistance in ovarian cancer.
- The Ag(I) complex shows preferential binding to DNA over RNA and higher affinity for non-canonical DNA structures compared to standard DNA.
Conclusions:
- The novel Ag(I)-biscarbene represents a promising new class of anticancer agents targeting non-canonical DNA structures.
- Its ability to overcome cisplatin resistance highlights its therapeutic potential.
- Further studies on its interactions with various biomolecular targets are warranted for a comprehensive understanding of its mechanism of action.
