Design and biological evaluation of novel water-soluble complexes based on thiosemicarbazone as prospective anticancer agents

The widespread success of platinum-based drugs in the clinical treatment of different neoplasia has led the inorganic metal complexes to be at the forefront of the fight against cancer. In this context, thiosemicarbazones and their metal derivatives serve as promising starting points for developing anticancer agents. In current study, the new fluorescent thiosemicarbazone ligand L and its complexes with some non-toxic first row transition metals such as Mn(II), Fe(III), Ni(II), Cu(II), and Zn(II) metal ions were attained as L^Mn, L^Fe, L^Ni, L^Cu, and L^Zn complexes. The molecular structures of the compounds were proved by chemico-physico techniques. The anti-proliferative activity of these compounds has been evaluated on human liposarcoma (SW-872) and human breast adenocarcinoma (MCF-7) using the MTT assay. The morphology of cell death and cell cycle studied in SW-872 cancerous cells was performed via flow cytometry. Eventually, imaging of treated cancerous cells with L^Mn and L^Zn complexes was performed by fluorescence microscopy. Compounds were designed in order to achieve a hydrophilic/lipophilic balance and synthesized through a condensation reaction. All compounds revealed high solubility in water and remained stable for more than 72 h in water as a neutral biological solvent. L^Mn and L^Zn complexes manifested good activity on SW-872 cancerous cells after 48 h exposure time ( IC₅₀: 134.8 ± 2.82 µg/mL and IC₅₀: 144.6 ± 2.07 µg/mL, respectively). The morphology of cell death in SW-872 cancerous cells treated with the L^Zn complex showed an apoptosis type cell death. Additionally, cell cycle studies declared the cell cycle arrest in the S phase for L^Zn. In conclusion, the development of water-soluble thiosemicarbazone complexes with intrinsic fluorescent properties promises to facilitate the detection of these compounds in living cells, aiding the investigation of their wide-ranging biological activities.