Synthesis, X-ray structure and cytotoxic effect of nickel(II) complexes with pyrazole ligands

• Published in: European journal of medicinal chemistry Vol. 46; no. 12; pp. 5917 - 5926
• Main Authors: Sobiesiak, Marta, Lorenz, Ingo-Peter, Mayer, Peter, Woźniczka, Magdalena, Kufelnicki, Aleksander, Krajewska, Urszula, Rozalski, Marek, Budzisz, Elzbieta
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Masson SAS 01.12.2011; Elsevier
• Subjects: Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biological and medical sciences; Cell Line, Tumor; Cell Survival - drug effects; Chelating Agents - chemical synthesis; Chelating Agents - chemistry; Chelating Agents - pharmacology; Coordination Complexes - chemical synthesis; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Crystallography, X-Ray; Cytotoxic effect; General aspects; Humans; Ligands; Medical sciences; Models, Molecular; Neoplasms - drug therapy; Nickel - chemistry; Nickel - pharmacology; Pharmacology. Drug treatments; Pyrazole ligands; Pyrazoles - chemical synthesis; Pyrazoles - chemistry; Pyrazoles - pharmacology; Synthesis; X-ray structure; Cytotoxic effect; Pyrazole ligands; Synthesis; X-ray structure; Antineoplastic agent; Divalent metal Complexes; Cytotoxicity; Thermal stability; Pyrazole derivatives; Chloro complex; Acute lymphocytic leukemia; Chemical synthesis; Tumor cell; Human; Promyelocytic leukemia; Melanoma; Organic ligand; Transition metal Complexes; In vitro; Biological activity; HL60 cell line; Protonation constant; Cell line; Aqua complex; Nickel II Complexes; Crystalline structure
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2011.10.001

Here we present the synthesis of the new Ni(II) complexes with chelating ligands 1-benzothiazol-2-yl-3,5-dimethyl-1 H-pyrazole ( a), 5-(2-hydroxyphenyl)-3-methyl-1-(2-pyridylo)-1 H-pyrazole-4-carboxylic acid methyl ester ( b) and 1-benzothiazol-2-yl-5-(2-hydroxyphenyl)-3-methyl-1 H-pyrazole-4-carboxylic acid methyl ester ( c). These ligands a– c create solid complexes with Ni(II). The crystal and molecular structures of two complexes were determined by X-ray diffraction method. Thermal stability of two complexes with ligand c by TG/DTG and DSC methods were also shown. Cytotoxic activity of all the complexes against three tumour cell lines and to normal endothelial cells (HUVEC) was also estimated. Complexes with ligand c exhibited relatively high cytotoxic activity towards HL-60 and NALM-6 leukaemia cells and WM-115 melanoma cells. Cytotoxic effectiveness of one of these complexes against melanoma WM-115 cells was two times higher than that of cisplatin. The protonation constant log K = 9.63 of ligand b corresponding to the phenol 2-hydroxy group has been determined in 10% (v/v) DMSO/water solution (25 °C). The coordination modes (formation of two monomeric species: NiL and NiL 2) in the complexes with Ni(II) are discussed for b on the basis of the potentiometric and UV/Vis data. New Ni(II) complexes with chelating ligands: 1-benzothiazol-2-yl-3,5-dimethyl-1 H-pyrazole ( a), 5-(2-hydroxybenzo-2-yl)-3-methyl-1-(2-pyridinyl)pyrazol-4-carboxylic acid methyl ester ( b) and 1-(2-benzothiazo-2-yl)-5-(2-hydroxyphenyl)-3-methyl-1 H-pyrazol-4-carboxylic acid methyl ester ( c) have been synthesized and characterized. Cytotoxic activity of their complexes 1a– c, 2a– c and 3c on tumour and normal cells are also shown. [Display omitted] ► X-ray crystal structures of Ni(II) complexes pyrazole-derived ligand. ► The complexing properties of pyrazole ligand b with Ni(II) in solution were examined. ► Cytotoxic effect of Ni(II) complexes against tumour and normal cells. ► Complex 1c showed higher cytotoxicity than cisplatin against melanoma WM-115 cells.