Akademik Veri Yönetim Sistemi
INORGANIC CHEMISTRY COMMUNICATIONS, cilt.189, 2026 (SCI-Expanded, Scopus)
In this study, novel Ni(II) mixed-ligand complexes derived from 3,5-dichlorosalicylaldehyde-S-methyl isothiosemicarbazone (H2L) and methyl-substituted pyridine co-ligands were synthesized and characterized. The complexes [NiL(Py)], [NiL(4-MePy)], [NiL(2,6-Me2Py)], and [NiL(2,4,6-Me3Py)] were obtained using pyridine derivatives with increasing methyl substitution. Structural characterization was performed by elemental analysis, FT-IR, UV-Vis, and 1H NMR spectroscopy, and the molecular structures of selected complexes were confirmed by single-crystal X-ray diffraction. DFT calculations provided geometric and electronic parameters consistent with experimental findings. The cytotoxic properties of the compounds were evaluated by MTT assay against MDA-MB-231, HCT-116, THP-1, and HUVEC cell lines. The results showed that complexation enhances cytotoxic activity compared to the free ligand. Among the series, [NiL(2,4,6-Me3Py)] exhibited the highest activity against MDA-MB-231 cells (IC50 = 2.7 mu M) together with lower toxicity toward HUVEC cells, indicating a degree of selectivity. Structure-activity relationship (SAR) analysis based on ADME parameters suggests that increasing methyl substitution on the pyridine co-ligands enhances lipophilicity, which may facilitate cellular uptake and contribute to improved cytotoxic effects. In addition, DNA-binding studies performed using UV-Vis and fluorescence spectroscopy indicated that the complexes are capable of interacting with DNA, suggesting a possible contribution of DNA binding to their cytotoxic effects. Molecular docking studies showed binding affinities consistent with cytotoxicity trends, although no direct biological validation was performed. Overall, the results indicate that these complexes exhibit promising in vitro cytotoxic profiles and warrant further mechanistic investigation.