1. NO Releasing and Anticancer Properties of Octahedral Ruthenium–Nitrosyl Complexes with Equatorial 1H-Indazole Ligands
- Author
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Vladimir B. Arion, Wee Han Ang, Ewelina Orlowska, Tara E. McDonnell, Maria V. Babak, Peter Rapta, Chinju Govind, Dominik Schaniel, Orsolya Dömötör, Venugopal Karunakaran, Michal Malček, Dominique Luneau, Éva A. Enyedy, Lukáš Bučinský, Yusuf Chouthury Shaik Farid, Michal Zalibera, Universität Wien, National University of Singapore (NUS), University of Szeged [Szeged], Slovak University of Technology in Bratislava, REQUIMTE/LAQV, Faculdade de Ciências, Universidade do Porto, National Institute for Interdisciplinary Science and Technology (CSIR), National Institute for Interdisciplinary Science and Technology [India], Nanyang Polytechnic - NYP (REPUBLIC OF SINGAPORE), School of Biotechnology and Biomolecular Sciences, University of New South Wales [Sydney] (UNSW), Laboratoire des Multimatériaux et Interfaces (LMI), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Cristallographie, Résonance Magnétique et Modélisations (CRM2), and Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Models, Molecular ,Indazoles ,Cell Survival ,Blotting, Western ,chemistry.chemical_element ,Antineoplastic Agents ,[CHIM.THER]Chemical Sciences/Medicinal Chemistry ,[CHIM.INOR]Chemical Sciences/Inorganic chemistry ,Ligands ,Nitric Oxide ,010402 general chemistry ,01 natural sciences ,Medicinal chemistry ,Ruthenium ,Inorganic Chemistry ,Inhibitory Concentration 50 ,chemistry.chemical_compound ,Deprotonation ,Drug Stability ,X-Ray Diffraction ,[CHIM.ANAL]Chemical Sciences/Analytical chemistry ,Electrochemistry ,Organometallic Compounds ,Acetone ,Humans ,Physical and Theoretical Chemistry ,Dichloromethane ,Indazole ,010405 organic chemistry ,Water ,HCT116 Cells ,0104 chemical sciences ,[CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry ,chemistry ,Octahedron ,Proton NMR ,Quantum Theory ,Nitrogen Oxides ,Cisplatin ,Cyclic voltammetry - Abstract
International audience; With the aim of enhancing the biological activity of ruthenium−nitrosyl complexes, new compounds with four equatorially bound indazole ligands, namely, trans-[RuCl(Hind) 4 (NO)]Cl 2 •H 2 O ([3]Cl 2 •H 2 O) and trans-[RuOH(Hind) 4 (NO)]Cl 2 •H 2 O ([4]Cl 2 •H 2 O), have been prepared from trans-[Ru(NO 2) 2 (Hind) 4 ] ([2]). When the pH-dependent solution behavior of [3]Cl 2 •H 2 O and [4]Cl 2 • H 2 O was studied, two new complexes with two deprotonated indazole ligands were isolated, namely [RuCl(ind) 2 (Hind) 2 (NO)] ([5]) and [RuOH(ind) 2 (Hind) 2 (NO)] ([6]). All prepared compounds were comprehensively characterized by spectroscopic (IR, UV−vis, 1 H NMR) techniques. Compound [2], as well as [3]Cl 2 •2(CH 3) 2 CO, [4]Cl 2 •2(CH 3) 2 CO, and [5]•0.8CH 2 Cl 2 , the latter three obtained by recrystallization of the first isolated compounds (hydrates or anhydrous species) from acetone and dichloromethane, respectively, were studied by X-ray diffraction methods. The photoinduced release of NO in [3]Cl 2 and [4]Cl 2 was investigated by cyclic voltammetry and resulting paramagnetic NO species were detected by EPR spectroscopy. The quantum yields of NO release were calculated and found to be low (3−6%), which could be explained by NO dissociation and recombination dynamics, assessed by femtosecond pump−probe spectroscopy. The geometry and electronic parameters of Ru species formed upon NO release were identified by DFT calculations. The complexes [3]Cl 2 and [4]Cl 2 showed considerable antiproliferative activity in human cancer cell lines with IC 50 values in low micromolar or submicromolar concentration range and are suitable for further development as potential anticancer drugs. p53-dependence of Ru−NO complexes [3]Cl 2 and [4]Cl 2 was studied and p53-independent mode of action was confirmed. The effects of NO release on the cytotoxicity of the complexes with or without light irradiation were investigated using NO scavenger carboxy-PTIO.
- Published
- 2018