Pyridazolate-bridged dicopper (II) SOD mimics with enhanced antiproliferative activities against estrogen and androgen independent cancer cell lines

The superoxide dismutase (SOD) mimicking potential of three pyridazolato-bridged copper complexes has been investigated by NBT assay. The lowest IC50 value observed for the SOD activity (3.90 × 10−7 M) for [Cu2{bis(3,6 pyrazol-1-yl)pyridazine}Cl4OH] · Cl (3) correlates well with its more facile Cu2+/Cu+ redox couple. These compounds exhibit remarkable antiproliferative activities against estrogen independent breast (BT-20) and androgen independent prostate cancer (PC-3) cell lines, respectively. The concentration of compound 3 that inhibits 50% of cell growth (IC50) after 96 h of treatment using MTT cell proliferation assay was found to be 1.73 μM in BT20 and 1.42 μM in PC3 cell line. Furthermore, compound 3 does have the ability to induce apoptosis in both cell lines after the treatment for 48 h. This effect is probably through generation of intracellular oxidative stress and induction of intrinsic apoptotic pathway.

Graphical abstractThe superoxide dismutase (SOD) mimicking potential of three pyridazolato-bridged copper complexes has been investigated by NBT assay. The lowest IC50 value observed for the SOD activity (3.90 × 10−7 M) for [Cu2{bis(3,6 pyrazol-1-yl)pyridazine}Cl4OH] · Cl (3) correlates well with its more facile Cu2+/Cu+ redox couple. These compounds exhibit remarkable antiproliferative activities against estrogen independent breast (BT-20) and androgen independent prostate cancer (PC-3) cell lines, respectively. Compound 3 has the ability to induce apoptosis in both cell lines after the treatment for 48 h.Figure optionsDownload full-size imageDownload as PowerPoint slide