Polycationic Monomeric and Homodimeric Asymmetric Monomethine Cyanine Dyes with Hydroxypropyl Functionality-Strong...

Area of Science:

• Medicinal Chemistry
• Biophysical Chemistry
• Molecular Biology

Background:

• Thiazole orange (TO) and thiazole orange homodimer (TOTO) are established cyanine dyes used in nucleic acid research.
• There is a need for novel cyanine dyes with enhanced properties and potential therapeutic applications.

Purpose of the Study:

• To synthesize new hydroxypropyl-functionalized analogs of TO and TOTO.
• To investigate the binding properties of these novel dyes with various nucleic acids.
• To evaluate their potential as theranostic agents.

Main Methods:

• Chemical synthesis of novel cyanine dye analogs.
• Spectroscopic studies (UV-Vis, fluorescence) to determine binding affinities.
• Circular dichroism (CD) titrations to assess dye-nucleic acid interactions.
• Cell-based assays to evaluate antiproliferative activity.

Main Results:

• Synthesized novel cyanine dyes demonstrated strong binding affinities (micromolar and submicromolar) to DNA ds-polynucleotides and poly rA-poly rU.
• The dyes exhibited selectivity for GC-DNA base pairs over AT-DNA, with enhanced fluorescence response.
• CD titrations revealed polynucleotide aggregation and supramolecular chirality; a dimer showed intercalation.
• The novel cyanine dyes displayed potent micromolar antiproliferative activity against cancer cell lines.

Conclusions:

• The new hydroxypropyl-functionalized cyanine dyes exhibit favorable nucleic acid binding properties and selectivity.
• These compounds possess significant antiproliferative activity, positioning them as promising candidates for theranostic applications in cancer treatment.