Ferrocenyl Paclitaxel and Docetaxel Derivatives: Impact of an Organometallic Moiety on the Mode of Action of Taxanes. Issue 32 (4th July 2016)

• Record Type: Journal Article
• Authors: Wieczorek, Anna; Błauż, Andrzej; Żal, Aleksandra; Arabshahi, Homayon John; Reynisson, Jóhannes; Hartinger, Christian G.; Rychlik, Błażej; Plażuk, Damian
• Is Part Of: Chemistry. Volume 22:Issue 32(2016)
• Page Start: 11413
• Page End: 11421
• Publication Date: 2016-07-04
• Subjects: bioorganometallic chemistry -- cancer -- medicinal chemistry -- microtubule -- tubulin polymerisation; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201601809
• Languages: English
• ISSNs: 0947-6539

Abstract

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. Abstract : A taxane effect : Ferrocenyl conjugates featuring the taxanes Paclitaxel and Docetaxel have been synthesised to exploit the influence of the organometallic moiety on their modes of action. Replacment of the N ‐benzoyl moiety by an N ‐ferrocenoyl group in Paclitaxel resulted in significantly enhanced cytotoxicity and ability to induce tubulin polymerisation in comparison with Paclitaxel.