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 ((1)H and (13)C) 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 IC(50) values range from 26 to 90nM, against all cell lines tested, while for cis-platin the IC(50) values range from 2 to 17microM and for the zinc salt, ZnCl(2), the IC(50) values range from 81 to 93microM. 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.
Stanojkovic
Tatjana P
TP
Institute for Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia.
Kovala-Demertzi
Dimitra
D
Primikyri
Alexandra
A
Garcia-Santos
Isabel
I
Castineiras
Alfonso
A
Juranic
Zorica
Z
Demertzis
Mavroudis A
MA
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects*; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013057:Spectrum Analysis / Q000379:methods; D013882:Thiosemicarbazones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015032:Zinc / Q000737:chemistry*
D000970:Antineoplastic Agents; D011725:Pyridines; D013882:Thiosemicarbazones; D015032:Zinc