Copper thiosemicarbazones: Antiproliferative action against C6 glioma cells

Abstract

2(E)-2-[1-(4-pyridinyl)ethylidene]hydrazinecarbothioammidehydrochloride (1) and two of its copper complexes were synthesized and structurally characterized. Cu(I) polymeric complex {[Cu(SCN)(3-Acpy)2]}n (2) was synthesized by in situ mixing of Cu(BF4)2.6H2O, 4-acetylpyridine (4-Acpy) and semicarbazide whereas a dinuclear Cu(II) complex (3) was obtained from the reaction of Cu(BF4)2.6H2O, 4-acetylpyridine and ammonium thiocyanate. Magnetic measurements were performed for the dinuclear complex. All the thiosemicarbazones were cytotoxic against malignant RT2 glioblastoma cells (expressing p53 protein) with IC50 values in the 5.1-13.2 µM range, and against malignant T98 glioblastoma cells (expressing mutant p53 protein) with IC50 values in the 4.5-31 µM range. Coordination to copper strongly increased the cytotoxic potential in complexes 2 and 3, when compared to that of free ligand and were found to be more potent than cisplatin. All the test compounds (1-3) were able to induce cell death by apoptosis.

Keywords

• Copper
• Glioma
• Thiosemicarbazones