Aryl ethynyl anthraquinones: a useful platform for targeting telomeric G-quadruplex structures

Area of Science:

• Medicinal Chemistry
• Molecular Biology
• Organic Synthesis

Background:

• Telomeric G-quadruplex structures are potential targets for therapeutic intervention.
• Anthraquinone derivatives have shown promise as DNA-interacting agents.
• Developing selective ligands for G-quadruplexes is crucial for therapeutic applications.

Purpose of the Study:

• To synthesize novel aryl ethynyl anthraquinones.
• To evaluate their potential as ligands for telomeric G-quadruplex DNA.
• To investigate how structural modifications influence binding and selectivity.

Main Methods:

• Sonogashira cross-coupling for synthesis.
• FRET melting assay for thermal stability.
• Circular dichroism for structural analysis.
• DNA synthesis arrest assay for biological activity.
• Molecular docking for binding mode prediction.

Main Results:

• Successful synthesis of aryl ethynyl anthraquinones.
• Demonstrated binding of synthesized compounds to telomeric G-quadruplexes.
• Established structure-activity relationships, showing that aryl ethynyl moiety structure controls binding and selectivity.
• Compounds exhibited selectivity for G-quadruplex over duplex DNA.

Conclusions:

• Aryl ethynyl anthraquinones are effective telomeric G-quadruplex ligands.
• The design of the aryl ethynyl moiety is a key factor in tuning ligand properties.
• These compounds represent a promising class for further investigation as G-quadruplex-targeting agents.