Intermolecular interactions between doxorubicin and β-cyclodextrin 4-methoxyphenol conjugates
Olga Swiech1, Anna Mieczkowska, Kazimierz Chmurski
1Department of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland.
The Journal of Physical Chemistry. B
|January 31, 2012
Summary
New cyclodextrin derivatives effectively bind the anticancer drug doxorubicin, forming stable inclusion complexes. This interaction
Area of Science:
- Supramolecular Chemistry
- Medicinal Chemistry
- Drug Delivery Systems
Background:
- Doxorubicin is a potent anticancer drug with significant adverse effects.
- Cyclodextrins are known for their ability to form inclusion complexes with drugs.
- Developing novel cyclodextrin derivatives can improve drug efficacy and reduce toxicity.
Purpose of the Study:
- To design and synthesize novel β-cyclodextrin derivatives as receptors for doxorubicin.
- To investigate the complexation behavior and stability of doxorubicin with these new derivatives.
- To explore the influence of solvent systems on the interaction modes between doxorubicin and cyclodextrin derivatives.
Main Methods:
- Synthesis of two new β-cyclodextrin derivatives: mono(6-deoxy-6-(1-1,2,3-triazo-4-yl)-1-propane-3-O-(4-methoxyphenyl))β-cyclodextrin (1) and mono(6-deoxy-6thio(1-propane-3-O-(4-methoxyphenyl))) β-cyclodextrin (2).
- Complexation studies using techniques such as cyclic voltammetry, UV-vis spectroscopy, and ¹H NMR.
- Molecular modeling to elucidate interaction mechanisms in different solvent systems (aqueous and DMSO).
Main Results:
- Doxorubicin formed inclusion complexes with both cyclodextrin derivatives (1 and 2) in aqueous and aqueous DMSO solutions.
- Complexation constants (K(s)) were significantly higher for the new derivatives (2.3 × 10⁴ and 3.2 × 10⁵ M⁻¹) compared to native β-cyclodextrin.
- The solvent system influenced the interaction mode: inclusion complex formation in aqueous media and hydrogen bonding/chloride ion association in pure DMSO.
Conclusions:
- The synthesized cyclodextrin derivatives demonstrate enhanced binding affinity for doxorubicin.
- The flexibility of the linker in the cyclodextrin side group contributes to the increased complex stability.
- The study highlights the crucial role of solvent environment in dictating drug-cyclodextrin interactions, offering potential for targeted drug delivery strategies.
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