6-Triazolyl-6-deoxy-β-cyclodextrin derivatives: synthesis, cellular toxicity, and phase-solubility study

Area of Science:

• Supramolecular Chemistry
• Medicinal Chemistry
• Carbohydrate Chemistry

Background:

• Cyclodextrins (CDs) are widely used due to their ability to form inclusion complexes.
• Modifying CDs can enhance their properties, such as water solubility and drug complexation.
• Triazole-modified CDs offer potential for improved pharmaceutical applications.

Purpose of the Study:

• To synthesize and characterize novel triazole-containing β-cyclodextrin derivatives.
• To evaluate the water solubility and cell viability of the new CD derivatives.
• To assess the potential of these derivatives in enhancing the solubility of poorly soluble drugs like prednisolone.

Main Methods:

• Copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) for synthesis.
• Nuclear Magnetic Resonance (NMR) spectroscopy for structural characterization.
• Water solubility tests, MTT assay for cell viability, and phase-solubility studies for drug complexation.

Main Results:

• Successful synthesis of heptakis{6-(4-hydroxymethyl-1H-[1,2,3]triazol-1-yl)-6-deoxy}-β-cyclodextrin (HTβCD) and heptakis{6-(4-sulfonylmethyl-1H-[1,2,3]triazol-1-yl)-6-deoxy}-β-cyclodextrin (STβCD).
• HTβCD and STβCD demonstrated at least 20-fold higher water solubility compared to native β-cyclodextrin.
• No adverse effects on cell viability were observed at 1mM concentrations.
• Significant enhancement of prednisolone solubility in the presence of increasing concentrations of HTβCD and STβCD.

Conclusions:

• The synthesized triazole-modified β-cyclodextrins (HTβCD and STβCD) possess superior water solubility.
• These novel CD derivatives are non-toxic at relevant concentrations.
• HTβCD and STβCD show promise for solubilizing poorly water-soluble drugs, particularly prednisolone.