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Synthesis and in vitro Biological Evaluation of Ferrocenyl Side-Chain-Functionalized Paclitaxel Derivatives

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cris.lastimport.scopus2024-02-12T20:29:51Z
dc.abstract.enTaxanes, including paclitaxel, are widely used in cancer therapy. In an attempt to overcome some of the disadvantages entailed with taxane chemotherapy, we devised the synthesis of ferrocenyl-functionalized paclitaxel derivatives and studied their biological properties. The cytotoxic activity was measured with a panel of human cancer cell lines of various tissue origin, including multidrug-resistant lines. A structure–activity study of paclitaxel ferrocenylation revealed the N-benzoyl-ferrocenyl-substituted derivative to be the most cytotoxic. In contrast, substitution of the 3′-phenyl group of paclitaxel with a ferrocenyl moiety led to less potent antiproliferative compounds. However, these agents were able to overcome multidrug resistance, as they were virtually unrecognized by ABCB1, a major cellular exporter of taxanes. Interestingly, the redox properties of these ferrocenyl derivatives appear to play a less important role in their mode of action, as there was no correlation between intracellular redox activity and cytotoxicity/cell-cycle distribution. The antiproliferative activity of ferrocenyl taxanes strongly depends on the substitution position, and good tubulin polymerization inducers, as confirmed by molecular docking, were usually more cytotoxic, whereas compounds with stronger pro-oxidative properties exhibited lower antiproliferative activity.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorEurtivon, Chatchakorn
dc.contributor.authorReynisson, Johannes
dc.contributor.authorArabshahi, Homayon
dc.contributor.authorBłauż, Andrzej
dc.contributor.authorPlażuk, Damian
dc.contributor.authorKowlaczyk, Karolina
dc.contributor.authorMakal, Anna
dc.contributor.authorHartinger, Christian
dc.contributor.authorPawlędzio, Sylwia
dc.contributor.authorWieczorek-Błauż, Anna
dc.contributor.authorRychlik, Błażej
dc.contributor.authorCiszewski, Wojciech
dc.date.accessioned2024-01-26T09:26:30Z
dc.date.available2024-01-26T09:26:30Z
dc.date.issued2017
dc.description.financeNie dotyczy
dc.description.number22
dc.description.volume12
dc.identifier.doi10.1002/CMDC.201700576
dc.identifier.issn1860-7179
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/121286
dc.identifier.weblinkhttps://chemistry-europe.onlinelibrary.wiley.com/doi/full/10.1002/cmdc.201700576
dc.languageeng
dc.pbn.affiliationchemical sciences
dc.relation.ispartofChemMedChem
dc.relation.pages1882-1892
dc.rightsClosedAccess
dc.sciencecloudnosend
dc.subject.enABCB1
dc.subject.enanticancer agents
dc.subject.enferrocenyl taxanes
dc.subject.enreactive oxygen species
dc.subject.entubulin polymerization
dc.titleSynthesis and in vitro Biological Evaluation of Ferrocenyl Side-Chain-Functionalized Paclitaxel Derivatives
dc.typeJournalArticle
dspace.entity.typePublication