Coumarin-Based Triapine Derivatives and Their Copper(II) Complexes: Synthesis, Cytotoxicity and mR2 RNR Inhibition Activity

A series of thiosemicarbazone-coumarin hybrids (HL1-HL3 and H2L4) has been synthesised in 12 steps used for the preparation mono- dinuclear copper(II) complexes, namely Cu(HL1)Cl2 (1), Cu(HL2)Cl2 (2), Cu(HL3)Cl2 (3) Cu2(H2L4)Cl4 (4), isolated hydrated or solvated forms. Both organic their dicopper(II) complexes were comprehensively characterised by analytical spectroscopic techniques, i.e., elemental analysis, ESI mass spectrometry, 1D 2D NMR, IR UV–vis spectroscopies, cyclic voltammetry (CV) spectroelectrochemistry (SEC). Re-crystallisation 1 from methanol afforded single crystals complex with monoanionic ligand Cu(L1)Cl, which could be studied crystal X-ray diffraction (SC-XRD). The prepared metal-free ligands revealed antiproliferative activity against highly resistant cancer cell lines, including triple negative breast cells MDA-MB-231, sensitive COLO-205 multidrug COLO-320 colorectal adenocarcinoma as well healthy human lung fibroblasts MRC-5 compared to those triapine doxorubicin. In addition, ability reduce tyrosyl radical mouse R2 protein ribonucleotide reductase ascertained EPR spectroscopy results triapine.