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Adjusting the Structure of β-Cyclodextrin to Improve Complexation of Anthraquinone-Derived Drugs

β-Cyclodextrin (CD) derivatives containing an aromatic triazole ring were studied as potential carriers of the following drugs containing an anthraquinone moiety: anthraquinone-2-sulfonic acid (AQ2S); anthraquinone-2-carboxylic acid (AQ2CA); and a common anthracycline, daunorubicin (DNR). UV-Vis and...

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Autores principales: Krzak, Agata, Swiech, Olga, Majdecki, Maciej, Garbacz, Piotr, Gwardys, Paulina, Bilewicz, Renata
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8659250/
https://www.ncbi.nlm.nih.gov/pubmed/34885787
http://dx.doi.org/10.3390/molecules26237205
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author Krzak, Agata
Swiech, Olga
Majdecki, Maciej
Garbacz, Piotr
Gwardys, Paulina
Bilewicz, Renata
author_facet Krzak, Agata
Swiech, Olga
Majdecki, Maciej
Garbacz, Piotr
Gwardys, Paulina
Bilewicz, Renata
author_sort Krzak, Agata
collection PubMed
description β-Cyclodextrin (CD) derivatives containing an aromatic triazole ring were studied as potential carriers of the following drugs containing an anthraquinone moiety: anthraquinone-2-sulfonic acid (AQ2S); anthraquinone-2-carboxylic acid (AQ2CA); and a common anthracycline, daunorubicin (DNR). UV-Vis and voltammetry measurements were carried out to determine the solubilities and association constants of the complexes formed, and the results revealed the unique properties of the chosen CDs as effective pH-dependent drug complexing agents. The association constants of the drug complexes with the CDs containing a triazole and lipoic acid (βCDLip) or galactosamine (βCDGAL), were significantly larger than that of the native βCD. The AQ2CA and AQ2S drugs were poorly soluble, and their solubilities increased as a result of complex formation with βCDLip and βCDGAL ligands. AQ2CA and AQ2S are negatively charged at pH 7.4. Therefore, they were less prone to form an inclusion complex with the hydrophobic CD cavity than at pH 3 (characteristic of gastric juices) when protonated. The βCDTriazole and βCDGAL ligands were found to form weaker inclusion complexes with the positively charged drug DNR at an acidic pH (pH 5.5) than in a neutral medium (pH 7.4) in which the drug dissociates to its neutral, uncharged form. This pH dependence is favorable for antitumor applications.
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spelling pubmed-86592502021-12-10 Adjusting the Structure of β-Cyclodextrin to Improve Complexation of Anthraquinone-Derived Drugs Krzak, Agata Swiech, Olga Majdecki, Maciej Garbacz, Piotr Gwardys, Paulina Bilewicz, Renata Molecules Article β-Cyclodextrin (CD) derivatives containing an aromatic triazole ring were studied as potential carriers of the following drugs containing an anthraquinone moiety: anthraquinone-2-sulfonic acid (AQ2S); anthraquinone-2-carboxylic acid (AQ2CA); and a common anthracycline, daunorubicin (DNR). UV-Vis and voltammetry measurements were carried out to determine the solubilities and association constants of the complexes formed, and the results revealed the unique properties of the chosen CDs as effective pH-dependent drug complexing agents. The association constants of the drug complexes with the CDs containing a triazole and lipoic acid (βCDLip) or galactosamine (βCDGAL), were significantly larger than that of the native βCD. The AQ2CA and AQ2S drugs were poorly soluble, and their solubilities increased as a result of complex formation with βCDLip and βCDGAL ligands. AQ2CA and AQ2S are negatively charged at pH 7.4. Therefore, they were less prone to form an inclusion complex with the hydrophobic CD cavity than at pH 3 (characteristic of gastric juices) when protonated. The βCDTriazole and βCDGAL ligands were found to form weaker inclusion complexes with the positively charged drug DNR at an acidic pH (pH 5.5) than in a neutral medium (pH 7.4) in which the drug dissociates to its neutral, uncharged form. This pH dependence is favorable for antitumor applications. MDPI 2021-11-27 /pmc/articles/PMC8659250/ /pubmed/34885787 http://dx.doi.org/10.3390/molecules26237205 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Krzak, Agata
Swiech, Olga
Majdecki, Maciej
Garbacz, Piotr
Gwardys, Paulina
Bilewicz, Renata
Adjusting the Structure of β-Cyclodextrin to Improve Complexation of Anthraquinone-Derived Drugs
title Adjusting the Structure of β-Cyclodextrin to Improve Complexation of Anthraquinone-Derived Drugs
title_full Adjusting the Structure of β-Cyclodextrin to Improve Complexation of Anthraquinone-Derived Drugs
title_fullStr Adjusting the Structure of β-Cyclodextrin to Improve Complexation of Anthraquinone-Derived Drugs
title_full_unstemmed Adjusting the Structure of β-Cyclodextrin to Improve Complexation of Anthraquinone-Derived Drugs
title_short Adjusting the Structure of β-Cyclodextrin to Improve Complexation of Anthraquinone-Derived Drugs
title_sort adjusting the structure of β-cyclodextrin to improve complexation of anthraquinone-derived drugs
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8659250/
https://www.ncbi.nlm.nih.gov/pubmed/34885787
http://dx.doi.org/10.3390/molecules26237205
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