Enhanced Stability and Bioactivity of Natural Anticancer Topoisomerase I Inhibitors through Cyclodextrin Complexation
| Autor: | Karen Orellana, Patrycja Michalska, Olmo Martín-Cámara, Víctor González-Ruiz, M. Antonia Martín, Víctor Cervera-Carrascón, Rafael León, Ángel Cores, J. Carlos Menéndez, Ana I. Olives |
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| Přispěvatelé: | Ministerio de Ciencia, Innovación y Universidades (España), Comunidad de Madrid, European Commission |
| Rok vydání: | 2021 |
| Předmět: |
Pharmaceutical Science
Protonation drug stabilization Article cavitands supramolecular complexes anticancer agents Tecnología farmaceútica Molecular recognition Pharmacy and materia medica medicine polycyclic compounds Química farmaceútica chemistry.chemical_classification Cyclodextrin technology industry and agriculture Química orgánica Nuclear magnetic resonance spectroscopy Combinatorial chemistry RS1-441 carbohydrates (lipids) chemistry Docking (molecular) Drug delivery molecular recognition Camptothecin Lactone medicine.drug |
| Zdroj: | E-Prints Complutense. Archivo Institucional de la UCM instname Pharmaceutics Volume 13 Issue 10 Pharmaceutics, Vol 13, Iss 1609, p 1609 (2021) Digital.CSIC. Repositorio Institucional del CSIC |
| Popis: | The use of cyclodextrins as drug nano-carrier systems for drug delivery is gaining impor-tance in the pharmaceutical industry due to the interesting pharmacokinetic properties of the resulting inclusion complexes. In the present work, complexes of the anti-cancer alkaloids camptothecin and luotonin A have been prepared with β-cyclodextrin and hydroxypropyl-β-cyclodextrin. These cy-clodextrin complexes were characterized by nuclear magnetic resonance spectroscopy (NMR). The variations in the H-NMR and C-NMR chemical shifts allowed to establish the inclusion modes of the compounds into the cyclodextrin cavities, which were supported by docking and molecular dynamics studies. The efficiency of the complexation was quantified by UV-Vis spectrophotom-etry and spectrofluorimetry, which showed that the protonation equilibria of camptothecin and luotonin A were drastically hampered upon formation of the inclusion complexes. The stabilization of camptothecin towards hydrolysis inside the cyclodextrin cavity was verified by the quantitation of the active lactone form by reverse phase liquid chromatography fluorimetric detection, both in basic conditions and in the presence of serum albumin. The antitumor activity of luotonin A and camptothecin complexes were studied in several cancer cell lines (breast, lung, hepatic carcinoma, ovarian carcinoma and human neuroblastoma) and an enhanced activity was found compared to the free alkaloids, particularly in the case of hydroxypropyl-β-cyclodextrin derivatives. This result shows that the cyclodextrin inclusion strategy has much potential towards reaching the goal of employing luotonin A or its analogues as stable analogues of camptothecin. This research was funded by grant RTI2018-097662-B-I00 from Ministerio de Ciencia, Innovación y Universidades, grant B2017/BMD-3813 from Comunidad Autónoma de Madrid (to JCM), grant PI17/01700 from IS Carlos III, co-financed by the European Regional Development funds (FEDER), and grant B2017/BMD-3827 from Comunidad Autónoma de Madrid (to RL). The APC was not funded. |
| Databáze: | OpenAIRE |
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