Exploring the Biological Efficacy of Zn(II)-Thiosemicarbazone-Ferrocene Complexes: In-Silico and In-Vitro Findings

With different N-terminal substitutions, three Zn(II) complexes (ZSL1-ZSL3) of ferrocene-linked thiosemicarbazone were developed. Several spectroscopic analyses were used to characterize the produced compounds. The ligand SL1 has a monoclinic crystal system of space group P2₁/n in single crystal XRD analysis. According to DNA binding tests conducted with UV-visible and fluorescence spectroscopy, ZSL1 was the strongest complex exhibiting a significant interaction with DNA (K_q = 3.56 × 10⁴ M^{− 1}, K_b = 3.86 × 10⁶ M^{− 1} & K_app = 3.33 × 10⁶ M^{− 1}). The BSA protein (ZSL1, which has a high K_b value of 7.98 × 10⁵ M^{− 1}) exhibits a similar binding tendency and ZSL1 highly influences the microenvironment of BSA protein evident from synchronous study. ZSL1 exhibits the strongest affinity for the epidermal growth factor receptor protein according to docking experiments, having a binding energy of ̶ 8.52 Kcal/mol. The Density Functional Theory studies take into consideration the complexes’ biological activity (ZSL1 possesses a higher biological activity because of its minimal value of electrophilicity index, 0.2264 eV) and stability (ZSL2 has greater stability of structure with a large band gap, 0.1370 eV). With a substantial IC₅₀ value of 34.6 ± 1.4 µM, the MTT test findings demonstrated that ZSL1 was the most efficient fighting complex toward human liver (HepG-2) cancer cell lines. Similarly, the cytotoxicity of the synthesized complexes was assessed in terms of MDA-MB-231 and MCF-7, two human breast cancer cell lines. The findings revealed that ZSL1 exhibits superior activity with IC₅₀ values of 20.84 ± 1.2 and 13.1 ± 1.1 µM, respectively. On the other hand, ZSL1 exhibited diminished cytotoxicity against normal human breast cell lines (MCF-10a) with an IC₅₀ of 63.9 ± 1.2 µM.