Description

• Title:
  Metal-Dependent Cytotoxic and Kinesin Spindle Protein Inhibitory Activity of Ru, Os, Rh, and Ir Half-Sandwich Complexes of IspinesibDerived Ligands
• Creator:
  Łomzik, Michał;
  Hanif, Muhammad;
  Budniok, Aleksandra;
  Blauz, Andrzej;
  Makal, Anna;
  Tchoń, Daniel M.;
  Leśniewska, Barbara;
  Tong, Kelvin K. H.;
  Movassaghi, Sanam;
  Söhnel, Tilo;
  Jamieson, Stephen M. F.;
  Zafar, Ayesha;
  Reynisson, Jóhannes;
  Rychlik, Błażej
• Contributor:
  Department of Organic Chemistry, Faculty of Chemistry, University of Łódź, ul. Tamka 12, 91-403 Łódź, Poland;
  School of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand;
  Cytometry Lab, Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Łódź, ul. Pomorska 141/143, 90-236 Łódź, Poland;
  Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, ul. Żwirki i Wigury 101, 02-089 Warszawa, Poland;;
  Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, ul. Żwirki i Wigury 101, 02-089 Warszawa, Poland;
  Faculty of Chemistry, University of Białystok, ul. K. Ciołkowskiego 1 K, 15-245 Białystok, Poland;
  Auckland Cancer Society Research Centre, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand;;
  School of Pharmacy and Bioengineering, Keele University, Hornbeam Building, Staffordshire ST5 5BG, United Kingdom;
  Cytometry Lab, Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Łódź, ul. Pomorska 141/143, 90-236 Łódź, Poland;
• Description:
  Ispinesib is a potent inhibitor of kinesin spindle protein (KSP), which has been identified as a promising target for antimitotic anticancer drugs. Herein, we report the synthesis of half-sandwich complexes of Ru, Os, Rh, and Ir bearing the ispinesib-derived N,N-bidentate ligands (R)- and (S)-2-(1-amino-2-methylpropyl)-3-benzyl-7-chloroquinazolin-4(3H)-one and studies on their chemical and biological properties. Using the enantiomerically pure (R)- and (S)-forms of the ligand, depending on the organometallic moiety, either the SM,R or RM,S diastereomers, respectively, were observed in the molecular structures of the Ru- and Os(cym) (cym = η6-p-cymene) compounds, whereas the RM,R or SM,S diastereomers were found for the Rh- and Ir(Cp*) (Cp* = η5-pentamethylcyclopentadienyl) derivatives. However, density functional theory (DFT) calculations suggest that the energy difference between the diastereomers is very small, and therefore a mixture of both will be present in solution. The organometallics exhibited varying antiproliferative activity in a series of human cancer cell lines, with the complexes featuring the (R)-enantiomer of the ligand being more potent than the (S)-configured counterparts. Notably, the Rh and Ir complexes demonstrated high KSP inhibitory activity, even at 1 nM concentration, which was independent of the chirality of the ligand, whereas the Ru and especially the Os derivatives were much less active.
• Object availability:
  free access
• Rights:
  Uznanie autorstwa 4.0 Międzynarodowe;
  http://creativecommons.org/licenses/by/4.0
• Date:
  2021.08.24;
  2020
• Type:
  Article
• Language:
  English
• Format:
  application/pdf
• Publisher:
  American Chemical Society
• Relation:
  Inorganic Chemistry;59
• Subject:
  metals;
  ligands;
  molecular structure;
  transition metals;
  nuclear magnetic resonance spectroscopy
• Identifier:
  0020-1669;
  http://hdl.handle.net/11089/38809 ;
  1520-510X;
  10.1021/acs.inorgchem.0c00957
• Data provider:
  Repozytorium Uniwersytetu Łódzkiego
• Can I use it?:
  check license
• Type:
  image