TY - JOUR
T1 - Coumarin-Based Triapine Derivatives and Their Copper(II) Complexes
T2 - Synthesis, Cytotoxicity and mR2 RNR Inhibition Activity
AU - Stepanenko, Iryna
AU - Babak, Maria V.
AU - Spengler, Gabriella
AU - Hammerstad, Marta
AU - Popovic‐Bijelic, Ana
AU - Shova, Sergiu
AU - Büchel, Gabriel E.
AU - Darvasiova, Denisa
AU - Rapta, Peter
AU - Arion, Vladimir B.
PY - 2021/6
Y1 - 2021/6
N2 - A series of thiosemicarbazone‐coumarin hybrids (HL1‐HL3 and H2L4) has been synthesised in 12 steps and used for the preparation of mono‐ and dinuclear copper(II) complexes, namely Cu(HL1)Cl2 (1), Cu(HL2)Cl2 (2), Cu(HL3)Cl2 (3) and Cu2(H2L4 )Cl4 (4), isolated in hydrated or solvated forms. Both the organic hybrids and their copper(II) and dicopper(II) complexes were comprehensively characterised by analytical and spectroscopic techniques, i.e., elemental analysis, ESI mass spectrometry, 1D and 2D NMR, IR and UV–vis spectroscopies, cyclic voltammetry (CV) and spectroelectrochemistry (SEC). Re‐crystallisation of 1 from methanol afforded single crystals of copper(II) complex with monoanionic ligand Cu(L1)Cl, which could be studied by single crystal X‐ray diffraction (SC‐XRD). The prepared copper(II) complexes and their metal‐free ligands revealed antiproliferative activity against highly resistant cancer cell lines, including triple negative breast cancer cells MDA‐MB‐231, sensitive COLO‐205 and multidrug resistant COLO‐320 colorectal adenocarcinoma cell lines, as well as in healthy human lung fibroblasts MRC‐5 and compared to those for triapine and doxorubicin. In addition, their ability to reduce the tyrosyl radical in mouse R2 protein of ribonucleotide reductase has been ascertained by EPR spectroscopy and the results were compared with those for triapine.
AB - A series of thiosemicarbazone‐coumarin hybrids (HL1‐HL3 and H2L4) has been synthesised in 12 steps and used for the preparation of mono‐ and dinuclear copper(II) complexes, namely Cu(HL1)Cl2 (1), Cu(HL2)Cl2 (2), Cu(HL3)Cl2 (3) and Cu2(H2L4 )Cl4 (4), isolated in hydrated or solvated forms. Both the organic hybrids and their copper(II) and dicopper(II) complexes were comprehensively characterised by analytical and spectroscopic techniques, i.e., elemental analysis, ESI mass spectrometry, 1D and 2D NMR, IR and UV–vis spectroscopies, cyclic voltammetry (CV) and spectroelectrochemistry (SEC). Re‐crystallisation of 1 from methanol afforded single crystals of copper(II) complex with monoanionic ligand Cu(L1)Cl, which could be studied by single crystal X‐ray diffraction (SC‐XRD). The prepared copper(II) complexes and their metal‐free ligands revealed antiproliferative activity against highly resistant cancer cell lines, including triple negative breast cancer cells MDA‐MB‐231, sensitive COLO‐205 and multidrug resistant COLO‐320 colorectal adenocarcinoma cell lines, as well as in healthy human lung fibroblasts MRC‐5 and compared to those for triapine and doxorubicin. In addition, their ability to reduce the tyrosyl radical in mouse R2 protein of ribonucleotide reductase has been ascertained by EPR spectroscopy and the results were compared with those for triapine.
KW - Antiproliferative activity
KW - Copper(II)
KW - Coumarin
KW - Electrochemistry
KW - Thiosemicarbazones
KW - Triapine
KW - Tyrosyl radical reduction
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UR - https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-85107436597&origin=recordpage
U2 - 10.3390/biom11060862
DO - 10.3390/biom11060862
M3 - RGC 21 - Publication in refereed journal
C2 - 34207929
SN - 2218-273X
VL - 11
JO - Biomolecules
JF - Biomolecules
IS - 6
M1 - 862
ER -
