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

Abstract

A novel fluorescent ligand (H₂LCl?1.5CH₃OH, 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)₂Cl₂ (2), Fe(HL)₂Cl₃?3H₂O (3), Ni(L)(HL)Cl?8H₂O (4), Cu(HL)Cl₂?4H₂O (5), Zn(H₂L)Cl₃ (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?μg/mL (35.66?±?0.56?μM) for SW-872 and 79.41?±?3.54?μg/mL (127.6?±?5.69?μM) 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.

Graphical abstract