Zn(II) complexes derived from S-alkyl thiosemicarbazones: Synthesis, characterization, DFT, and antiproliferative, cytotoxic, antimigratory effects on human lung and breast cancer
Inorganic Chemistry Communications, cilt.191, sa.P2, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 191 Sayı: P2
- Basım Tarihi: 2026
- Doi Numarası: 10.1016/j.inoche.2026.117072
- Dergi Adı: Inorganic Chemistry Communications
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, Chimica, DIALNET
- Anahtar Kelimeler: Cytotoxicity, DFT, Frontier molecular orbitals, Single-crystal, Thiosemicarbazone, Zinc(II) complex
- Yozgat Bozok Üniversitesi Adresli: Evet
Özet
Six novel Zn(II) complexes (ZnL1–ZnL6) derived from S-alkyl thiosemicarbazone ligands were synthesized via template condensation and characterized by FT-IR, UV–Vis, 1H NMR, and 13C NMR spectroscopy. The molecular structure of ZnL4 was further confirmed by single-crystal X-ray diffraction analysis, revealing a distorted square-pyramidal coordination geometry around the Zn(II) center.Density functional theory (DFT) calculations revealed a significant reduction in the HOMO–LUMO energy gap upon coordination, indicating enhanced electronic delocalization and increased electrophilicity. TD-DFT results supported the experimental absorption spectra, confirming π → π* and intraligand charge-transfer transitions. Nonlinear optical (NLO) analysis showed that ZnL1 and ZnL6 exhibited the highest hyperpolarizability (β) values, suggesting efficient intramolecular charge transfer (ICT) and strong electronic polarization.The zinc–ligand complexes (ZnL1–ZnL6) were evaluated for their antiproliferative, cytotoxic, and antimigratory activities against human lung and breast cancer cell lines and non-malignant epithelial cells. Cell viability was measured using the MTT assay to determine GI₅₀ and IC₅₀ values; cytotoxicity was assessed through LDH release; and migration was tested using the scratch wound-healing assay. Most complexes showed strong growth inhibition at low micromolar concentrations, with H1650 cells being the most sensitive. IC₅₀ values for non-cancerous cells were significantly higher, resulting in favorable tumor selectivity indices for several compounds, especially ZnL1, ZnL3, and ZnL6. LDH release was low to moderate, indicating limited membrane damage, while migration was notably reduced in highly motile cancer cells.Overall, Zn(II) coordination appears to alter the electronic structure and enhance electrophilic character, which may contribute to the observed antiproliferative and antimigratory activities, suggesting a possible correlation between molecular structure, electronic properties, and biological performance. These findings highlight the potential of Zn(II)-based thiosemicarbazone complexes as promising candidates for the development of selective anticancer agents.