caa a22 4500 605506957 CHVBK 20210128100629.0 cr unu---uuuuu 210128e20150101xx s 000 0 eng 10.1007/s00775-014-1217-3 doi (NATIONALLICENCE)springer-10.1007/s00775-014-1217-3 Novel Platinum(II) compounds modulate insulin-degrading enzyme activity and induce cell death in neuroblastoma cells [Elektronische Daten] [Grazia Tundo, Diego Sbardella, Sandra De Pascali, Chiara Ciaccio, Massimo Coletta, Francesco Fanizzi, Stefano Marini] The properties of three novel Platinum(II) compounds toward the insulin-degrading enzyme (IDE) enzymatic activity have been investigated under physiological conditions. The rationale of this study resides on previous observations that these compounds, specifically designed and synthesized by some of us, induce apoptosis in various cancer cell lines, whereas IDE has been proposed as a putative oncogene involved in neuroblastoma onset and progression. Two of these compounds, namely [PtCl(O,O′-acac)(DMSO)] and [Pt(O,O′-acac)(γ-acac)(DMS)], display a modulatory behavior, wherefore activation or inhibition of IDE activity occurs over different concentration ranges (suggesting the existence of two binding sites on the enzyme). On the other hand, [Pt(O,O′-acac)(γ-acac)(DMSO)] shows a typical competitive inhibitory pattern, characterized by a meaningful affinity constant (K i =0.95±0.21μM). Although all three compounds induce cell death in neuroblastoma SHSY5Y cells at concentrations exceeding 2μM, the two modulators facilitate cells' proliferation at concentrations≤1.5μM, whereas the competitive inhibitor [Pt(O,O′-acac)(γ-acac)(DMSO)] only shows a pro-apoptotic activity at all investigated concentrations. These features render the [Pt(O,O′-acac)(γ-acac)(DMSO)] a promising "lead compound” for the synthesis of IDE-specific inhibitors (not characterized yet) with therapeutic potentiality. SBIC, 2014 Insulin-degrading enzyme nationallicence Cisplatin nationallicence Neuroblastoma nationallicence Platinum(II) compounds nationallicence Tundo Grazia Department of Clinical Sciences and Translational Medicine, University of Roma Tor Vergata, Via Montpellier 1, 00133, Rome, Italy aut Sbardella Diego Department of Clinical Sciences and Translational Medicine, University of Roma Tor Vergata, Via Montpellier 1, 00133, Rome, Italy aut De Pascali Sandra CIRCMSB, Via C. Ulpiani 27, 70125, Bari, Italy aut Ciaccio Chiara Department of Clinical Sciences and Translational Medicine, University of Roma Tor Vergata, Via Montpellier 1, 00133, Rome, Italy aut Coletta Massimo Department of Clinical Sciences and Translational Medicine, University of Roma Tor Vergata, Via Montpellier 1, 00133, Rome, Italy aut Fanizzi Francesco CIRCMSB, Via C. Ulpiani 27, 70125, Bari, Italy aut Marini Stefano Department of Clinical Sciences and Translational Medicine, University of Roma Tor Vergata, Via Montpellier 1, 00133, Rome, Italy aut JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/1(2015-01-01), 101-108 0949-8257 20:1<101 2015 20 775 https://doi.org/10.1007/s00775-014-1217-3 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00775-014-1217-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Tundo Grazia Department of Clinical Sciences and Translational Medicine, University of Roma Tor Vergata, Via Montpellier 1, 00133, Rome, Italy aut NATIONALLICENCE 700 1- Sbardella Diego Department of Clinical Sciences and Translational Medicine, University of Roma Tor Vergata, Via Montpellier 1, 00133, Rome, Italy aut NATIONALLICENCE 700 1- De Pascali Sandra CIRCMSB, Via C. Ulpiani 27, 70125, Bari, Italy aut NATIONALLICENCE 700 1- Ciaccio Chiara Department of Clinical Sciences and Translational Medicine, University of Roma Tor Vergata, Via Montpellier 1, 00133, Rome, Italy aut NATIONALLICENCE 700 1- Coletta Massimo Department of Clinical Sciences and Translational Medicine, University of Roma Tor Vergata, Via Montpellier 1, 00133, Rome, Italy aut NATIONALLICENCE 700 1- Fanizzi Francesco CIRCMSB, Via C. Ulpiani 27, 70125, Bari, Italy aut NATIONALLICENCE 700 1- Marini Stefano Department of Clinical Sciences and Translational Medicine, University of Roma Tor Vergata, Via Montpellier 1, 00133, Rome, Italy aut NATIONALLICENCE 773 0- JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/1(2015-01-01), 101-108 0949-8257 20:1<101 2015 20 775