title: Ferrocenyl Paclitaxel and Docetaxel Derivatives: Impact of an Organometallic Moiety on the Mode of Action of Taxanes.
abstract: A series of ferrocenyl analogues and derivatives of paclitaxel and docetaxel were synthesised and assayed for their antiproliferative/cytotoxic effects, impact on the cell cycle distribution and ability to induce tubulin polymerisation. The replacement of the 3'-N-benzoyl group of paclitaxel with a ferrocenoyl moiety, in particular, led to formation of an analogue that was at least one order of magnitude more potent in terms of antiproliferative activity than the parent compound (IC50 values of 0.11 versus 1.11 μm, respectively), but still preserved the classical taxane mode of action, that is, microtubule stabilisation leading to mitotic arrest. Molecular docking studies revealed an unexpected binding pocket in the tubulin structure for the ferrocenoyl group introduced in the paclitaxel backbone.
authors.affiliation: Department of Organic Chemistry, Faculty of Chemistry, University of Łódź, Tamka 12, 41-403, Łódź, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Wieczorek
authors.affiliation: Cytometry Lab, Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Łódź, ul. Pomorska 141/143, 90-236, Łódź, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Błauż
authors.affiliation: Cytometry Lab, Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Łódź, ul. Pomorska 141/143, 90-236, Łódź, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Żal
authors.affiliation: School of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
authors.forename: Homayon John
authors.initials: HJ
authors.lastname: Arabshahi
authors.affiliation: School of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
authors.forename: Jóhannes
authors.initials: J
authors.lastname: Reynisson
authors.affiliation: School of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
authors.forename: Christian G
authors.identifier: http://orcid.org/0000-0001-9806-0893
authors.initials: CG
authors.lastname: Hartinger
authors.affiliation: Cytometry Lab, Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Łódź, ul. Pomorska 141/143, 90-236, Łódź, Poland. brychlik@biol.uni.lodz.pl.
authors.forename: Błażej
authors.identifier: http://orcid.org/0000-0001-8928-5900
authors.initials: B
authors.lastname: Rychlik
authors.affiliation: Department of Organic Chemistry, Faculty of Chemistry, University of Łódź, Tamka 12, 41-403, Łódź, Poland. damplaz@uni.lodz.pl.
authors.forename: Damian
authors.identifier: http://orcid.org/0000-0002-2898-6604
authors.initials: D
authors.lastname: Plażuk
mesh_terms: D002453:Cell Cycle / Q000187:drug effects*; D000077143:Docetaxel; D006801:Humans; D062105:Molecular Docking Simulation; D009942:Organometallic Compounds / Q000737:chemistry*; D017239:Paclitaxel / Q000737:chemistry* / Q000378:metabolism; D043823:Taxoids / Q000737:chemistry* / Q000378:metabolism; D014404:Tubulin / Q000737:chemistry* / Q000378:metabolism
chemical_list: D009942:Organometallic Compounds; D043823:Taxoids; D014404:Tubulin; D000077143:Docetaxel; D017239:Paclitaxel
keywords: bioorganometallic chemistry; cancer; medicinal chemistry; microtubule; tubulin polymerisation