A novel water-soluble thiosemicarbazone Schiff base ligand and its complexes as potential anticancer agents and cellular fluorescence imaging

A novel fluorescent ligand (H2LCl center dot 1.5CH(3)OH, 1) was synthesized and metal complexes of 1 with Mn(II), Fe(III), Ni(II), Cu(II), and Zn(II) were obtained as Mn(HL)(2)Cl-2 (2), Fe(HL)(2)Cl-3 center dot 3H(2)O (3), Ni(L)(HL)Cl center dot 8H(2)O (4), Cu(HL)Cl-2 center dot 4H(2)O (5), Zn(H2L)Cl-3 (6), respectively. These compounds were identified by spectroscopic methods, elemental analysis, molar conductivity, and single-crystal X-ray crystallography. According to the crystal structure of 4 nickel (II), center is surrounded by two ligands in a distorted octahedral geometry. The ligand and its complexes are soluble in water and have excellent stability. In vitro anti-proliferative activity of these compounds was evaluated against human breast adenocarcinoma (MCF-7) and human lipo-sarcoma (SW-872) as cancer cells and human fibroblasts (HFF-2) as normal cells by MTT assay. Interestingly, complex 5 exhibited excellent activity against both cancer cells with low IC50 value 22.18 +/- 0.35 mu g/ mL (35.66 +/- 0.56 mu M) for SW-872 and 79.41 +/- 3.54 mu g/mL (127.6 +/- 5.69 mu M) for MCF-7 among the compounds and in comparison with paclitaxel (PTX) which acts finely. Morphological changes were evaluated by flow cytometry that revealed apoptosis is the main cause of cell death. Likewise, cell cycle studies indicated the cell cycle arrest in the -G1 and S phases for complex 5 against MCF-7 and SW-872 cancer cells, while complex 6 could arrest the MCF- 7 and SW-872 cells in -G2 and -G1 phases, respectively. All of the compounds are fluorescent which enabled us to monitor the uptake and intracellular distribution in living human cancer cells by fluorescence microscopy. [GRAPHICS] .

Automated summary

A novel fluorescent ligand was synthesized and complexed with various metal ions. The resulting compounds showed excellent solubility and stability in water. One of the complexes exhibited potent anti-proliferative activity against breast adenocarcinoma and liposarcoma cells, and its mechanism of action was determined through cell cycle and flow cytometry analysis.