A ruthenium(II) polypyridyl complex disrupts actin cytoskeleton assembly and blocks cytokinesis

Gill, Martin R., Jarman, Paul J., Hearnden, Vanessa, Fairbanks, Simon D., Bassetto, Marcella, Palmer, John, Ayscough, Kathryn R., Thomas, Jim A. and Smythe, Carl 2022. A ruthenium(II) polypyridyl complex disrupts actin cytoskeleton assembly and blocks cytokinesis. Angewandte chemie-international edition 61 (27) , e202117449. 10.1002/anie.202117449

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Abstract

The dinuclear RuII complex [(Ru(phen)2)2(tpphz)]4+ (phen=1,10-phenanthroline, tpphz=tetrapyridophenazine) “RuRuPhen” blocks the transformation of G-actin monomers to F-actin filaments with no disassembly of pre-formed F-actin. Molecular docking studies indicate multiple RuRuPhen molecules bind to the surface of G-actin but not the binding pockets of established actin polymerisation inhibitors. In cells, addition of RuRuPhen causes rapid disruption to actin stress fibre organisation, compromising actomyosin contractility and cell motility; due to this effect RuRuPhen interferes with late-stage cytokinesis. Immunofluorescent microscopy reveals that RuRuPhen causes cytokinetic abscission failure by interfering with endosomal sorting complexes required for transport (ESCRT) complex recruitment.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Date of First Compliant Deposit:	28 February 2023
Date of Acceptance:	13 April 2022
Last Modified:	03 May 2023 08:54
URI:	https://orca.cardiff.ac.uk/id/eprint/157345

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