Synthesis, cytotoxicity, and long-term single dose anti-cancer pharmacological evaluation of dimethyltin(IV) complex of N(4)-methylthiosemicarbazone (having ONS donor ligand)

Background and Objective: Toxicity of the chemotherapeutic compounds is widely investigated. An organotin (IV) derivative was designed to modulate the toxicity and long-term anticancer efficacy of the single dose. Materials and Methods: The reaction of dimethyltin(IV) dichloride with N(4)-methylthiosemicarbazone derived by condensation of 4-methylthiosemicarbazone with 5-bromo-2-hydroxybenzaldehyde was prepared in 1:1 M ratio in absolute methanol. The newly synthesized complex was characterized by elemental analysis, FT-IR, electronic, and 1H, 13C and 119Sn NMR spectroscopy. In vitro cytotoxicity (MTT, (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide)), anticancer (migration, clonogenic, 3D tumor aggregation, nucleus condensation and mitochondrial membrane potential) activity, and in silico QSAR and molecular docking studies were performed. Results: The title compound was observed to be potent and selective toxic against MCF-7, HCT-116, and A549 human cancer cell lines. Moreover, this derivative was found to be less-cytotoxic and higher cytostatic at the single dose than other organotin (IV) complexes due to modulation of chelation of ligand with Sn(IV) ion. The anticancer activities against A549 cancer cells, however, were only moderate. The reason for this could be due to inhibition of enzymatic reaction in the cells for glucose uptake, DNA and protein synthesis. Discussion and Conclusion: The resonance impact of aromatic rings, hydrogen bonding, and ROS reduction, NO generation, caspase induction showed potential impact to the cancer cell apoptosis, antimigration, and inhibition of tumor aggregation of this compound.