Synthesis of small molecules targeting multiple DNA structures using click chemistry

Area of Science:

• Medicinal Chemistry
• Molecular Biology
• DNA Structures

Background:

• Small molecules targeting DNA are crucial in cancer therapy.
• Acridine derivatives are a known class of DNA-interacting agents.

Purpose of the Study:

• To synthesize and evaluate novel 9-aminoacridine carboxamides.
• To investigate their binding affinities to various DNA tertiary structures.
• To assess their antiproliferative activity against cancer cell lines.

Main Methods:

• Click chemistry for synthesis of monomeric and dimeric acridine carboxamides.
• DNA binding assays for duplex, quadruplex, and four-way junction DNA.
• Antiproliferative assays using the HL60 cell line.

Main Results:

• Monomeric 3-carboxamides effectively stabilized G-quadruplex DNA and four-way junctions.
• Acridine dimers exhibited complex structure-activity relationships.
• Compounds showed varying correlations between DNA binding and antiproliferative activity.

Conclusions:

• Novel acridine carboxamides demonstrate potential as antitumour agents.
• Specific structural features influence DNA binding and biological activity.
• The compounds' effects on DNA junction structures may impact interactions with Holliday junction-binding proteins.