4338-47-0Relevant articles and documents
Bioactivation of food genotoxicants 5-hydroxymethylfurfural and furfuryl alcohol by sulfotransferases from human, mouse and rat: a comparative study
Sachse, Benjamin,Meinl, Walter,Sommer, Yasmin,Glatt, Hansruedi,Seidel, Albrecht,Monien, Bernhard H.
, p. 137 - 148 (2016)
5-Hydroxymethylfurfural (HMF) and furfuryl alcohol (FFA) are moderately potent rodent carcinogens that are present in thermally processed foodstuffs. The carcinogenic effects were hypothesized to originate from sulfotransferase (SULT)-mediated bioactivation yielding DNA-reactive and mutagenic sulfate esters, a confirmed metabolic pathway of HMF and FFA in mice. It is known that orthologous SULT forms substantially differ in substrate specificity and tissue distribution. This could influence HMF- and FFA-induced carcinogenic effects. Here, we studied HMF and FFA sulfoconjugation by 30 individual SULT forms of humans, mice and rats. The catalytic efficiencies (kcat/KM) of HMF sulfoconjugation of human SULT1A1 (13.7?s?1?M?1), mouse Sult1a1 (15.8?s?1?M?1) and 1d1 (4.8?s?1?M?1) and rat Sult1a1 (5.3?s?1?M?1) were considerably higher than those of all other SULT forms investigated (≤0.73?s?1M?1). FFA sulfoconjugation was monitored using adenosine as a nucleophilic scavenger for the reactive 2-sulfoxymethylfuran (t1/2?=?20?s at 37?°C). The resulting adduct N6-((furan-2-yl)methyl)-adenosine (N6-MF-A) was quantified by isotope-dilution UPLC-MS/MS. The rates of N6-MF-A formation showed that hSULT1A1 and its orthologues in mice and rats were also the most important contributors to FFA sulfoconjugation in each of the species. Taken together, the catalytic capacity of hSULT1A1 is comparable to that of mSult1a1 in mice, the species in which carcinogenic effects of HMF and FFA were detected. This is of primary concern due to the expression of hSULT1A1 in many different tissues.
Multinuclear magnetic resonance characterization and antiproliferative studies of novel dichlorido platinum(II) complexes containing kinetin riboside and 1-β-D-ribofuranosyl-4-(2-pyridyl)-1H-1,2,3-triazole
Jakubowski, Mateusz,?akomska, Iwona,Sitkowski, Jerzy,Pokrywczyńska, Marta,D?browski, Pawe?,Framski, Grzegorz,Ostrowski, Tomasz
, (2020/02/15)
The chemical reaction between cis-[PtCl2(dmso)2] and kinetin riboside (KR) or 1-β-D-ribofuranosyl-4-(2-pyridyl)-1H-1,2,3-triazole (PTR) has resulted in two novel platinum(II) complexes being obtained with different compositions of the coordination sphere: cis-[PtCl2(PTR)] (1) and cis-[PtCl2(dmso)(KR)] (2). Based on multinuclear NMR results (1H, 13C, 15N, 195Pt), we have demonstrated that the N-donor ligands PTR and KR are able to coordinate to the Pt(II) ion as bidentate via two nitrogen atoms (N(3) and N(7)) or monodentate via only one nitrogen atom (N(7)), respectively. On the other hand, biological studies showed that the novel platinum(II) complexes exhibit different in vitro cytotoxicity towards A549 (lung carcinoma epithelial cells), T24 (urinary bladder cancer cells) and CRL1872 (malignant melanoma cells). The complex cis-[PtCl2(dmso)(KR)] (2) shows in vitro cytotoxicity against T24 and CRL1872 cell lines (the IC50 parameters amount to 52.2 μM and 21.4 μM, respectively), whereas cis-[PtCl2(PTR)] (1) is not able to inhibit a proliferation of these cells in the range of tested concentrations.
Kinetin Riboside and Its ProTides Activate the Parkinson’s Disease Associated PTEN-Induced Putative Kinase 1 (PINK1) Independent of Mitochondrial Depolarization
Osgerby, Laura,Lai, Yu-Chiang,Thornton, Peter J.,Amalfitano, Joseph,Le Duff, Cécile S.,Jabeen, Iqra,Kadri, Hachemi,Miccoli, Ageo,Tucker, James H. R.,Muqit, Miratul M. K.,Mehellou, Youcef
, p. 3518 - 3524 (2017/05/05)
Since loss of function mutations of PINK1 lead to early onset Parkinson’s disease, there has been growing interest in the discovery of small molecules that amplify the kinase activity of PINK1. We herein report the design, synthesis, serum stability, and hydrolysis of four kinetin riboside ProTides. These ProTides, along with kinetin riboside, activated PINK1 in cells independent of mitochondrial depolarization. This highlights the potential of modified nucleosides and their phosphate prodrugs as treatments for neurodegenerative diseases.
