DNA Binding and Anticancer Activity of Tetrazole-Based Schiff Bases and Their Platinum (II) Complexes <i>via In Vitro</i> and <i>In Silico</i> Endpoints

In this study, new low-toxicity tetrazole-based Schiff bases and their Pt(II) complexes were synthesized. The cytotoxicity profiles of the ligands and their Pt(II) complexes were evaluated using the WST-1 proliferation assay in healthy (Human umbilical vein endothelial cells [HUVEC]) and cancerous (Human lung adenocarcinoma, A549, and Human cervical carcinoma [HeLa]) cell lines, with cisplatin used as a reference drug. While the ligands exhibited negligible cytotoxicity, the Pt(II) complexes demonstrated moderate cytotoxic effects, with [Pt(Tet-SalCl)] showing higher potency than [Pt(Tet-SalH)]. To investigate the mechanism of cytotoxicity, in vitro calf thymus DNA (Ct-DNA) interaction studies and in silico molecular docking analyses were conducted. As a preliminary toxicity profiling step, in silico LD50 predictions were performed, yielding values of 747.416 mg/kg for (Tet-SalH) and 940.3818 mg/kg for (Tet-SalCl), supporting the low-toxicity profile of the synthesized ligands. Overall, this work presents the synthesis, characterization, and cytotoxic evaluation of novel low-toxicity ligands and their Pt(II) complexes, which, while showing slightly different activity and DNA interaction profiles compared to cisplatin at equivalent concentrations, demonstrate comparable behavior and underscore their promising therapeutic potential.