title: Increasing anti-cancer activity with longer tether lengths of group 9 Cp* complexes.
abstract: Here in, we report the cytotoxicity of both rhodium and iridium functionalised Cp* analogues of the [Cp*MCl2]2 dimers. The functionalised dimers contain a hydroxy tethered arm of differing carbon length. These show promising IC50 values when tested against HT-29, A2780 and cisplatin-resistant A2780cis human cancer cell lines, with the cytotoxicity improving proportionally with an increase in carbon tether length of the Cp* ring. The most promising results are seen for the 14-carbon Cp* tethered rhodium () and iridium () complexes, which show up to a 24-fold increase in IC50 compared to the unfunctionalised [Cp*MCl2]2 dimer. All complexes were potent inhibitors of purified thioredoxin reductase suggesting that disruption of cellular anti-oxidant function is one potential mechanism of action.
authors.affiliation: School of Chemistry, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK. p.c.mcgowan@leeds.ac.uk.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Lucas
authors.affiliation: School of Chemistry, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK. p.c.mcgowan@leeds.ac.uk.
authors.forename: Rianne M
authors.initials: RM
authors.lastname: Lord
authors.affiliation: School of Chemistry, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK. p.c.mcgowan@leeds.ac.uk.
authors.forename: Aida M
authors.initials: AM
authors.lastname: Basri
authors.affiliation: Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield, HD1 3DH, UK.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Allison
authors.affiliation: Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield, HD1 3DH, UK.
authors.forename: Roger M
authors.initials: RM
authors.lastname: Phillips
authors.affiliation: School of Chemistry, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK. p.c.mcgowan@leeds.ac.uk.
authors.forename: A John
authors.initials: AJ
authors.lastname: Blacker
authors.affiliation: School of Chemistry, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK. p.c.mcgowan@leeds.ac.uk.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: McGowan
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D007495:Iridium / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology*; D012238:Rhodium / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D007495:Iridium; D012238:Rhodium; D002945:Cisplatin