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• W4306803445 endingPage "17312" @default.
• W4306803445 startingPage "17299" @default.
• W4306803445 abstract "The mitochondrial calcium uniporter (MCU) is a transmembrane protein that resides on the inner membrane of the mitochondria and mediates calcium uptake into this organelle. Given the critical role of mitochondrial calcium trafficking in cellular function, inhibitors of this channel have arisen as tools for studying the biological relevance of this process and as potential therapeutic agents. In this study, four new analogues of the previously reported Ru-based MCU inhibitor [ClRu(NH3)4(μ-N)Ru(NH3)4Cl]Cl3 (Ru265) are reported. These compounds, which bear axial carboxylate ligands, are of the general formula [(RCO2)Ru(NH3)4(μ-N)Ru(NH3)4(O2CR)]X3, where X = NO3- or CF3SO3- and R = H (1), CH3 (2), CH2CH3 (3), and (CH2)2CH3 (4). These complexes were fully characterized by IR spectroscopy, NMR spectroscopy, and elemental analysis. X-ray crystal structures of 1 and 3 were obtained, revealing the expected presence of both the linear Ru(μ-N)Ru core and axial formate and propionate ligands. The axial carboxylate ligands of complexes 1-4 are displaced by water in buffered aqueous solution to give the aquated compound Ru265'. The kinetics of these processes were measured by 1H NMR spectroscopy, revealing half-lives that span 5.9-9.9 h at 37 °C. Complex 1 with axial formate ligands underwent aquation approximately twice as fast as the other compounds. In vitro cytotoxicity and mitochondrial membrane potential measurements carried out in HeLa and HEK293T cells demonstrated that none of these four complexes negatively affects cell viability or mitochondrial function. The abilities of 1-4 to inhibit mitochondrial calcium uptake in permeabilized HEK293T cells were assessed and compared to that of Ru265. Fresh solutions of 1-4 are approximately 2-fold less potent than Ru265 with IC50 values in the range of 14.7-19.1 nM. Preincubating 1-4 in aqueous buffers for longer time periods to allow for the aquation reactions to proceed increases their potency of mitochondrial uptake inhibition to match that of Ru265. This result indicates that 1-4 are aquation-activated prodrugs of Ru265'. Finally, 1-4 were shown to inhibit mitochondrial calcium uptake in intact, nonpermeabilized cells, revealing their value as tools and potential therapeutic agents for mitochondrial calcium-related disorders." @default.
• W4306803445 created "2022-10-20" @default.
• W4306803445 creator A5020494357 @default.
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• W4306803445 date "2022-10-19" @default.
• W4306803445 modified "2023-09-27" @default.
• W4306803445 title "Carboxylate-Capped Analogues of Ru265 Are MCU Inhibitor Prodrugs" @default.
• W4306803445 cites W1173363010 @default.
• W4306803445 cites W1485297825 @default.
• W4306803445 cites W1493374490 @default.
• W4306803445 cites W1510224559 @default.
• W4306803445 cites W1515322105 @default.
• W4306803445 cites W1550056692 @default.
• W4306803445 cites W1969360633 @default.
• W4306803445 cites W1969709153 @default.
• W4306803445 cites W1979103494 @default.
• W4306803445 cites W1986213783 @default.
• W4306803445 cites W1990769348 @default.
• W4306803445 cites W1991036925 @default.
• W4306803445 cites W1998780196 @default.
• W4306803445 cites W2002352450 @default.
• W4306803445 cites W2010572143 @default.
• W4306803445 cites W2025894603 @default.
• W4306803445 cites W2042721486 @default.
• W4306803445 cites W2047402237 @default.
• W4306803445 cites W2062458432 @default.
• W4306803445 cites W2064495674 @default.
• W4306803445 cites W2067841051 @default.
• W4306803445 cites W2076184497 @default.
• W4306803445 cites W2083354933 @default.
• W4306803445 cites W2084226635 @default.
• W4306803445 cites W2085554856 @default.
• W4306803445 cites W2088265030 @default.
• W4306803445 cites W2088335558 @default.
• W4306803445 cites W2092581425 @default.
• W4306803445 cites W2092808769 @default.
• W4306803445 cites W2093439904 @default.
• W4306803445 cites W2109427445 @default.
• W4306803445 cites W2128270335 @default.
• W4306803445 cites W2128497087 @default.
• W4306803445 cites W2131350133 @default.
• W4306803445 cites W2132415639 @default.
• W4306803445 cites W2136340210 @default.
• W4306803445 cites W2139989763 @default.
• W4306803445 cites W2147626588 @default.
• W4306803445 cites W2148103576 @default.
• W4306803445 cites W2149346447 @default.
• W4306803445 cites W2159560452 @default.
• W4306803445 cites W2169682503 @default.
• W4306803445 cites W2203908584 @default.
• W4306803445 cites W2209823888 @default.
• W4306803445 cites W2289081179 @default.
• W4306803445 cites W2343726927 @default.
• W4306803445 cites W2514452289 @default.
• W4306803445 cites W2514802762 @default.
• W4306803445 cites W2592052735 @default.
• W4306803445 cites W2735703446 @default.
• W4306803445 cites W2741843627 @default.
• W4306803445 cites W2761046827 @default.
• W4306803445 cites W2794867021 @default.
• W4306803445 cites W2804791770 @default.
• W4306803445 cites W2808739989 @default.
• W4306803445 cites W2810777483 @default.
• W4306803445 cites W2846941494 @default.
• W4306803445 cites W2877383832 @default.
• W4306803445 cites W2882326707 @default.
• W4306803445 cites W2885025259 @default.
• W4306803445 cites W2908467301 @default.
• W4306803445 cites W2943983020 @default.
• W4306803445 cites W2951049173 @default.
• W4306803445 cites W2995347224 @default.
• W4306803445 cites W3005116495 @default.
• W4306803445 cites W3006611984 @default.
• W4306803445 cites W3007527235 @default.
• W4306803445 cites W3009265606 @default.
• W4306803445 cites W3016810220 @default.
• W4306803445 cites W3020819774 @default.
• W4306803445 cites W3026314418 @default.
• W4306803445 cites W3049005351 @default.
• W4306803445 cites W3081231770 @default.
• W4306803445 cites W3082505046 @default.
• W4306803445 cites W3134501520 @default.
• W4306803445 cites W3165224062 @default.
• W4306803445 cites W3177177104 @default.
• W4306803445 cites W358640895 @default.
• W4306803445 cites W4200413646 @default.
• W4306803445 cites W4211187268 @default.
• W4306803445 cites W4243240123 @default.
• W4306803445 cites W4255760236 @default.
• W4306803445 cites W4289260784 @default.
• W4306803445 doi "https://doi.org/10.1021/acs.inorgchem.2c02930" @default.
• W4306803445 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36260092" @default.
• W4306803445 hasPublicationYear "2022" @default.
• W4306803445 type Work @default.

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