Selenium-Substituted Monomethine Cyanine Dyes as Selective G-Quadruplex Spectroscopic Probes with Theranostic...

Area of Science:

• Medicinal Chemistry
• Molecular Biology
• Biophysical Chemistry

Background:

• Cyanine dyes are versatile fluorescent molecules with potential applications in diagnostics and therapeutics.
• Understanding their interactions with various nucleic acid structures is crucial for developing targeted therapies.

Purpose of the Study:

• To evaluate the binding interactions of novel benzoselenazolyl-containing monomethine cyanine dyes with duplex DNA, RNA, and G-quadruplex structures.
• To assess the impact of different substituents on cyanine dye selectivity and biological activity.
• To explore the theranostic potential of these cyanine dyes.

Main Methods:

• Fluorescence spectroscopy
• UV/Vis spectroscopy (thermal melting)
• Circular dichroism (CD) spectroscopy
• Cell viability assays
• Confocal microscopy

Main Results:

• Monomethine cyanine dyes with methyl substituents demonstrated 100-fold selectivity for G-quadruplex over duplex DNA.
• Cyanine dyes bind to G-quadruplex via end π-π stacking and groove interactions.
• A thioethyl-substituted cyanine could distinguish between duplex DNA, RNA, and G-quadruplex structures.
• Methyl-substituted cyanines showed submicromolar anticancer activity against human cancer cell lines.
• Substituent-dependent cellular localization was observed: sulfopropyl/thioethyl in mitochondria, methyl in the nucleus/nucleolus.

Conclusions:

• The studied cyanine dyes exhibit selective G-quadruplex binding and potent anticancer activity.
• Substituent modification influences nucleic acid selectivity, cellular localization, and biological effects.
• These findings highlight the potential of these cyanine derivatives as theranostic agents.