Zinc(II) complexes of 2-acetyl pyridine 1-(4-fluorophenyl)-piperazinyl thiosemicarbazone: Synthesis, spectroscopic study and crystal structures – Potential anticancer drugs

2-Acetyl pyridine thiosemicarbazone containing an 1-(4-fluorophenyl)-piperazinyl ring incorporated at N(4)-position, HAcPipPheF (1) and the zinc(II) complexes [Zn(AcPipPheF)2] (2) and [Zn(OAc)(AcPipPheF)]2 (3) have been prepared and structurally characterized by means of vibrational and NMR (1H and 13C) spectroscopy. The crystal structures of the compounds 1–3 have been determined by X-ray crystallography. The metal coordination geometry of [Zn(AcPipPheF)2] is described as distorted octahedral configuration in a trans-N–cis-N–cis-S configuration. In [Zn(OAc)(AcPipPheF)]2 one of the acetato group exhibits monoatomic bridge and the other bridges in a bidentate manner. The zinc(1) metal ion is coordinated in a distorted octahedral configuration while the metal coordination of Zn(2) is described as distorted square pyramidal. Biomedical studies revealed that, compounds 1–3 displayed potent anticancer activity. The antiproliferative activity of 1–3 was found to be considerably stronger than that of cis-platin. The IC50 values range from 26 to 90 nM, against all cell lines tested, while for cis-platin the IC50 values range from 2 to 17 μM and for the zinc salt, ZnCl2, the IC50 values range from 81 to 93 μM. The complex 3 shows the highest activity against all four cancer cell lines and the highest selectivity against K562 and MDA-MB-453 cancer cell lines. The compounds inhibited tumor cell proliferation by arresting the cell cycle progression at the S phase.

Graphical abstract2-Acetyl pyridine thiosemicarbazone containing an 1-(4-fluorophenyl)-piperazinyl ring incorporated at N(4)-position, HAcPipPheF (1) and the Zinc(II) complexes [Zn(AcPipPheF)2] (2) and [Zn(OAc)(AcPipPheF)]2 (3) have been prepared and structurally characterized by means of vibrational and NMR (1H and 13C) spectroscopy. The crystal structures of the compounds 1-3 have been determined by X-ray crystallography. Biomedical studies revealed that, compounds 1–3 displayed potent anticancer activity. The antiproliferative activity of 1–3 was found to be considerably stronger than that of cis-platin. The IC50 values range from 26 to 90 nM, against all cell lines tested, while for cis-platin the IC50 values range from 2 to 17 μM and for the Zinc salt, ZnCl2, the IC50 values range from 81 to 93 μM. The complex 3 shows the highest activity against all four cancer cell lines and the highest selectivity against K562 and MDA-MB-453 cancer cell lines. The compounds inhibited tumor cell proliferation by arresting the cell cycle progression at the S phase.Figure optionsDownload full-size imageDownload as PowerPoint slide