Synthesis, characterization and cytotoxic activity of binuclear copper(II)-complexes with some S-isoalkyl derivatives of thiosalicylic acid. Crystal structure of the binuclear copper(II)-complex with S-isopropyl derivative of thiosalicylic acid

Isoalkyl (isoalkyl = isopropyl-(L1), isobutyl-(L2) and isoamyl-(L3)) derivatives of thiosalicylic acid (TSA) were prepared by alkylation of TSA with corresponding isoalkyl-chlorides in the alkaline water-ethanol solution. The new free copper(II)-complexes with corresponding S-isoalkyl derivatives of TSA (C1-copper(II)-complex with S-isopropyl derivative of thiosalicylic acid, C2-copper(II)-complex with S-isobutyl derivative of thiosalicylic acid and C3-copper(II)-complex with S-isoamyl derivative of thiosalicylic acid) have been synthesized by direct reaction of copper(II)-nitrate with ligand precursor and then characterized by microanalysis, infrared spectra (IR) and EPR (electron paramagnetic resonance) spectra. The spectroscopically predicted structure of the obtained binuclear copper(II)-complex with S-isopropyl derivative of thiosalicylic acid was confirmed by X-ray analysis. Single crystals suitable for X-ray measurements were obtained by slow crystallization from a water solution. Newly synthesized precursors S-isoalkyl derivatives of thiosalicylic acid and corresponding copper(II)-complexes moderately reduced viability of human and murine lung cancer cells, they showed similar cytotoxic effect on human colorectal cancer cells as cisplatin and lower cytotoxic effect than cisplatin toward normal fibroblasts, evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) colorimetric technique. All new complexes exhibited apoptotic effect toward lung cancer cells, stronger than cisplatin, whereas only C3 induced significant apoptosis of colorectal cancer cells. Complex C1 showed significant antiproliferative effect against murine lung cancer cells, LLC1, while C2 reduced expression of Ki67 in human colorectal cancer cells. All tested complexes induced cell cycle arrest of HCT116 cells in G2/M phase.