Investigations on Antiproliferative Potential of Thiosemicarbazone Zn(II) Complexes: Design, Synthesis, and Density Functional Theory Studies on Structural Parameters

Zinc complexes have promising possibilities as medicines since they have better efficacy and lower toxicity. Herein, two ligands are synthesized based on hydrazine‐1‐carbothioamide with substituents having different electronic nature {nitro (HNPhHCT) and methoxy (HMoPhHCT) } and their respective Zn(II) complexes { [Zn(NPhHCT) 2 ] and [Zn(MoPhHCT) 2 ] }. They have been fully characterized via several spectroscopic techniques (IR, NMR, HRMS, UV–Vis studies) and DFT studies. In addition, ligands and their respective complexes are screened for their antiproliferative activity against three different cancer cell lines, namely HuT‐78 (T‐cell lymphoma), DL (Dalton's lymphoma), and MCF‐7 (Breast cancer) cell lines. Among the two complexes, [Zn(MoPhHCT) 2 ] is found to be most cytotoxic on all three cancer cell lines. In HuT‐78 cells, [Zn(MoPhHCT) 2 ] exhibited IC 50 value at ≈4 µM. Further, glucose and ROS estimation assays suggested that [Zn(MoPhHCT) 2 ] shows antiproliferative activity against T lymphoma cells by inhibiting their glycolytic activity and apoptosis induction by increasing ROS production. A molecular docking study is performed against an antiapoptotic protein, BCL2 (PDB: 2O2F), that confirms its inhibitory response with a binding score of −8.34 kcal mol −1 . Further, the expression of BCL2 at the protein level is found to be significantly inhibited in response to treatment with [Zn(MoPhHCT) 2 ] , as evident by the Western blot analysis results.