Mapping the interactions and bioactivity of quercetin-(2-hydroxypropyl)-β-cyclodextrin complex

Area of Science:

• Medicinal Chemistry
• Natural Product Chemistry
• Drug Discovery

Background:

• Natural products are vital for drug discovery but often suffer from poor aqueous solubility, limiting their bioavailability and therapeutic application.
• The integration of natural products into drug discovery pipelines has declined due to bioavailability challenges.
• Quercetin (QUE), a natural product, exhibits promising bioactivity but has poor aqueous solubility.

Purpose of the Study:

• To synthesize and characterize a quercetin (QUE)-(2-hydroxypropyl)-β-cyclodextrin (HP-β-CD) complex.
• To enhance the aqueous solubility and bioavailability of quercetin.
• To confirm the retention of quercetin's bioactivity in a T24 human bladder cancer cell line.

Main Methods:

• Complexation of quercetin with (2-hydroxypropyl)-β-cyclodextrin.
• Solubility and bioactivity assays in T24 human bladder cancer cells.
• Analytical techniques including 2D DOSY NMR and high-resolution NMR spectroscopy.
• Molecular Dynamics (MD) simulations to elucidate complex stability and molecular interactions.

Main Results:

• The synthesized QUE-HP-β-CD complex demonstrated significantly enhanced aqueous solubility compared to free QUE.
• NMR spectroscopy confirmed the formation of an inclusion complex, with specific interactions involving the aromatic rings of QUE.
• Bioactivity assays showed that the complex retained the therapeutic efficacy of QUE in T24 human bladder cancer cells.
• MD simulations corroborated the experimental findings, providing insights into the host-guest interactions.

Conclusions:

• The QUE-HP-β-CD complex effectively overcomes the solubility limitations of quercetin, a valuable natural product.
• This complexation strategy enhances bioavailability while preserving the inherent bioactivity of quercetin.
• The developed complex holds potential for improved drug delivery and therapeutic applications of natural products.