Structural studies and biological activity of the new Ni(II), Cu(II), Zn(II), Pd(II), and Ag(I) thiosemicarbazone-based complexes

Abstract

Three new chloro-substituted nitrophenyl-based thiosemicarbazones, namely: HTSC-oCl, HTSC-mCl, and HTSC-pCl (where HTSC-Cl = N-chlorophenyl-2-[(4-nitrophenyl)methylidene]hydrazine-1-carbothioamide; −o/−m/−p = −ortho/−meta/−para), and fifteen of their Ni(II), Cu(II), Zn(II), Pd(II) and Ag(I) complexes were synthesized and studied in terms of physicochemical properties and biological activity. All three ligands and six complexes were studied using single crystal X-ray diffraction analysis, revealing the N,S-binding mode and deprotonation of the organic ligand. Of all compounds, Cu(TSC-oCl)₂, Cu(TSC-mCl)₂, and Pd(TSC-oCl)₂ exhibited the best anticancer activity on LN-229 and T-47D, reaching IC₅₀ values equal to 2.64 ± 0.57 μM, 1.65 ± 0.14 μM, and 1.52 ± 0.12 μM, respectively. The mechanism of action studies revealed distinct characteristics for Cu(II) and Pd(II) complexes, with Cu(TSC-oCl)₂ and Cu(TSC-mCl)₂ strongly activating antioxidant genes and acting as potent ROS producers, while Pd(TSC-oCl)₂ appears to successfully target the cells' DNA. Most importantly, all three complexes were less toxic toward healthy BJ cells. In addition to that, several bacteria strains: S. aureus, S. epidermidis, B. subtilis, and E. coli were found to be susceptible toward some of the tested complexes, particularly those based on Cu(II), Zn(II), Pd(II), and Ag(I), with MIC values reaching 6.25 mg/L.