Enhanced Stability and Bioactivity of Natural Anticancer Topoisomerase I Inhibitors through Cyclodextrin Complexation

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dc.contributor.authorGonzález Ruiz, Víctor
dc.contributor.authorCores Esperón, Ángel
dc.contributor.authorMartín Cámara, Olmo
dc.contributor.authorSerrano Orellana, Karen
dc.contributor.authorMichalska Dziama, Patrycja
dc.contributor.authorCervera Carrascón, Víctor Enrique
dc.contributor.authorLeón Martínez, Rafael
dc.contributor.authorOlives Barba, Ana Isabel
dc.contributor.authorMartín Carmona, María Antonia
dc.contributor.authorMenéndez Ramos, José Carlos
dc.date.accessioned2023-06-16T14:22:19Z
dc.date.available2023-06-16T14:22:19Z
dc.date.issued2021-10-03
dc.description.abstractThe use of cyclodextrins as drug nano-carrier systems for drug delivery is gaining importance 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 cyclodextrin complexes were characterized by nuclear magnetic resonance spectroscopy (NMR). The variations in the 1H-NMR and 13C-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 spectrophotometry 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.
dc.description.departmentDepto. de Química en Ciencias Farmacéuticas
dc.description.facultyFac. de Farmacia
dc.description.refereedTRUE
dc.description.sponsorshipMinisterio de Ciencia e Innovación (España)
dc.description.sponsorshipComunidad de Madrid
dc.description.sponsorshipInstituto de Salud Carlos III
dc.description.sponsorshipFederación Española de Enfermedades Raras
dc.description.statuspub
dc.eprint.idhttps://eprints.ucm.es/id/eprint/71806
dc.identifier.citationGonzález-Ruiz, Víctor, et al. «Enhanced Stability and Bioactivity of Natural Anticancer Topoisomerase I Inhibitors through Cyclodextrin Complexation». Pharmaceutics, vol. 13, n.o 10, octubre de 2021, p. 1609. DOI.org (Crossref), https://doi.org/10.3390/pharmaceutics13101609.
dc.identifier.doi10.3390/pharmaceutics13101609
dc.identifier.issn1999-4923
dc.identifier.officialurlhttps://doi.org/10.3390/pharmaceutics13101609
dc.identifier.relatedurlhttp://www.mdpi.com/journal/pharmaceutics
dc.identifier.urihttps://hdl.handle.net/20.500.14352/4851
dc.issue.number10
dc.journal.titlePharmaceutics
dc.language.isoeng
dc.page.initial1609
dc.publisherMDPI
dc.relation.projectIDinfo:eu-repo/grantAgreement/RTI2018-097662-B-I00
dc.relation.projectIDinfo:eu-repo/grantAgreement/B2017/BMD-3813
dc.relation.projectIDinfo:eu-repo/grantAgreement/B2017/BMD-3827)PI17/01700
dc.relation.projectIDinfo:eu-repo/grantAgreement/B2017/BMD-3827
dc.rightsAtributtion 4.0 International
dc.rights.accessRightsopen access
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subject.cdu615.4
dc.subject.keywordMolecular recognition
dc.subject.keywordCavitands
dc.subject.keywordSupramolecular complexes
dc.subject.keywordAnticancer agents
dc.subject.keywordDrug stabilization
dc.subject.ucmQuímica farmaceútica
dc.subject.ucmQuímica orgánica (Farmacia)
dc.subject.ucmTecnología farmaceútica
dc.subject.unesco2390 Química Farmacéutica
dc.titleEnhanced Stability and Bioactivity of Natural Anticancer Topoisomerase I Inhibitors through Cyclodextrin Complexation
dc.typejournal article
dc.volume.number13
dspace.entity.typePublication
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