FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2246766813> ?p ?o ?g. }

• W2246766813 endingPage "e0137800" @default.
• W2246766813 startingPage "e0137800" @default.
• W2246766813 abstract "Differential redox homeostasis in normal and malignant cells suggests that pro-oxidant-induced upregulation of cellular reactive oxygen species (ROS) should selectively target cancer cells without compromising the viability of untransformed cells. Consequently, a pro-oxidant deviation well-tolerated by nonmalignant cells might rapidly reach a cell-death threshold in malignant cells already at a high setpoint of constitutive oxidative stress. To test this hypothesis, we took advantage of a selected number of amine-pyridine-based Fe(II) complexes that operate as efficient and robust oxidation catalysts of organic substrates upon reaction with peroxides. Five of these Fe(II)-complexes and the corresponding aminopyridine ligands were selected to evaluate their anticancer properties. We found that the iron complexes failed to display any relevant activity, while the corresponding ligands exhibited significant antiproliferative activity. Among the ligands, none of which were hemolytic, compounds 1, 2 and 5 were cytotoxic in the low micromolar range against a panel of molecularly diverse human cancer cell lines. Importantly, the cytotoxic activity profile of some compounds remained unaltered in epithelial-to-mesenchymal (EMT)-induced stable populations of cancer stem-like cells, which acquired resistance to the well-known ROS inducer doxorubicin. Compounds 1, 2 and 5 inhibited the clonogenicity of cancer cells and induced apoptotic cell death accompanied by caspase 3/7 activation. Flow cytometry analyses indicated that ligands were strong inducers of oxidative stress, leading to a 7-fold increase in intracellular ROS levels. ROS induction was associated with their ability to bind intracellular iron and generate active coordination complexes inside of cells. In contrast, extracellular complexation of iron inhibited the activity of the ligands. Iron complexes showed a high proficiency to cleave DNA through oxidative-dependent mechanisms, suggesting a likely mechanism of cytotoxicity. In summary, we report that, upon chelation of intracellular iron, the pro-oxidant activity of amine-pyrimidine-based iron complexes efficiently kills cancer and cancer stem-like cells, thus providing functional evidence for an efficient family of redox-directed anti-cancer metallodrugs." @default.
• W2246766813 created "2016-06-24" @default.
• W2246766813 creator A5008387911 @default.
• W2246766813 creator A5011546162 @default.
• W2246766813 creator A5012910968 @default.
• W2246766813 creator A5038561689 @default.
• W2246766813 creator A5041077017 @default.
• W2246766813 creator A5042906007 @default.
• W2246766813 creator A5045599657 @default.
• W2246766813 creator A5058412649 @default.
• W2246766813 creator A5060312863 @default.
• W2246766813 creator A5077509011 @default.
• W2246766813 creator A5081445092 @default.
• W2246766813 date "2015-09-14" @default.
• W2246766813 modified "2023-10-18" @default.
• W2246766813 title "Pro-Oxidant Activity of Amine-Pyridine-Based Iron Complexes Efficiently Kills Cancer and Cancer Stem-Like Cells" @default.
• W2246766813 cites W1489844805 @default.
• W2246766813 cites W1490655572 @default.
• W2246766813 cites W1592286099 @default.
• W2246766813 cites W1965788245 @default.
• W2246766813 cites W1969451624 @default.
• W2246766813 cites W1969524738 @default.
• W2246766813 cites W1971372405 @default.
• W2246766813 cites W1977373583 @default.
• W2246766813 cites W1978438460 @default.
• W2246766813 cites W1980763538 @default.
• W2246766813 cites W1981182593 @default.
• W2246766813 cites W1985233650 @default.
• W2246766813 cites W1989187489 @default.
• W2246766813 cites W1989824509 @default.
• W2246766813 cites W1990645562 @default.
• W2246766813 cites W1991442202 @default.
• W2246766813 cites W1999356404 @default.
• W2246766813 cites W2000718634 @default.
• W2246766813 cites W2009447754 @default.
• W2246766813 cites W2014691022 @default.
• W2246766813 cites W2017119076 @default.
• W2246766813 cites W2021018103 @default.
• W2246766813 cites W2021568546 @default.
• W2246766813 cites W2022471892 @default.
• W2246766813 cites W2023546573 @default.
• W2246766813 cites W2028897202 @default.
• W2246766813 cites W2035880310 @default.
• W2246766813 cites W2037731850 @default.
• W2246766813 cites W2040850983 @default.
• W2246766813 cites W2041851797 @default.
• W2246766813 cites W2041897873 @default.
• W2246766813 cites W2043276068 @default.
• W2246766813 cites W2046451859 @default.
• W2246766813 cites W2047758994 @default.
• W2246766813 cites W2050102962 @default.
• W2246766813 cites W2050259170 @default.
• W2246766813 cites W2055367666 @default.
• W2246766813 cites W2058569154 @default.
• W2246766813 cites W2062107099 @default.
• W2246766813 cites W2062727392 @default.
• W2246766813 cites W2069748048 @default.
• W2246766813 cites W2072648963 @default.
• W2246766813 cites W2073268419 @default.
• W2246766813 cites W2076655264 @default.
• W2246766813 cites W2077165807 @default.
• W2246766813 cites W2077813812 @default.
• W2246766813 cites W2083753857 @default.
• W2246766813 cites W2089811590 @default.
• W2246766813 cites W2094068415 @default.
• W2246766813 cites W2095715114 @default.
• W2246766813 cites W2097233535 @default.
• W2246766813 cites W2109772186 @default.
• W2246766813 cites W2110345152 @default.
• W2246766813 cites W2113594381 @default.
• W2246766813 cites W2118758371 @default.
• W2246766813 cites W2120656656 @default.
• W2246766813 cites W2123250752 @default.
• W2246766813 cites W2127277747 @default.
• W2246766813 cites W2127431843 @default.
• W2246766813 cites W2133782048 @default.
• W2246766813 cites W2140126848 @default.
• W2246766813 cites W2141874177 @default.
• W2246766813 cites W2144576921 @default.
• W2246766813 cites W2159640574 @default.
• W2246766813 cites W2160951862 @default.
• W2246766813 cites W2161339168 @default.
• W2246766813 cites W2166499489 @default.
• W2246766813 cites W2169647073 @default.
• W2246766813 cites W2169934255 @default.
• W2246766813 cites W2171559922 @default.
• W2246766813 doi "https://doi.org/10.1371/journal.pone.0137800" @default.
• W2246766813 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4569415" @default.
• W2246766813 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26368127" @default.
• W2246766813 hasPublicationYear "2015" @default.
• W2246766813 type Work @default.
• W2246766813 sameAs 2246766813 @default.
• W2246766813 citedByCount "27" @default.
• W2246766813 countsByYear W22467668132016 @default.
• W2246766813 countsByYear W22467668132017 @default.
• W2246766813 countsByYear W22467668132018 @default.
• W2246766813 countsByYear W22467668132019 @default.
• W2246766813 countsByYear W22467668132020 @default.

• next