Synthesis, characterization and biological evaluation of newly designed silver(I)-N-heterocyclic carbene (NHC) complexes
Results in Chemistry, cilt.27, 2026 (ESCI, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 27
- Basım Tarihi: 2026
- Doi Numarası: 10.1016/j.rechem.2026.103400
- Dergi Adı: Results in Chemistry
- Derginin Tarandığı İndeksler: Emerging Sources Citation Index (ESCI), Scopus, Directory of Open Access Journals
- Anahtar Kelimeler: ADMET profiling, Breast cancer, Chemotherapy, Cytotoxicity, Selectivity index, Silver(I)-N-heterocyclic carbene complexes
- Sivas Cumhuriyet Üniversitesi Adresli: Evet
Özet
In this study, a new series of silver(I) N -heterocyclic carbene (NHC) complexes was rationally designed, synthesized, and systematically evaluated for their anticancer efficacy against breast carcinoma cell lines. Structural diversification was achieved through deliberate ligand modification: complex 1 incorporates a phenyl substituent, complex 2 a benzoyl moiety, while complexes 3 and 4 feature nitro- and fluoro-substituted benzoyl groups, respectively, to fine-tune steric and electronic parameters. Cytotoxicity assays in T47D, MCF-7, and MDA-MB-231 cell lines revealed the highest sensitivity in T47D (IC₅₀ = 8.01–10.41 μM), lower responsiveness in MCF-7 (12.66–23.86 μM), and moderate sensitivity in MDA-MB-231 (15.16–36.17 μM). Notably, complex 2 showed the greatest potency (IC₅₀ = 8.01 ± 1.61 μM), highlighting the key role of ligand design in cytotoxic activity. Selectivity index (SI) values for all complexes were > 1 on T47D cells, indicating preferential toxicity toward cancer cells, with complex 1 showing slightly higher selectivity. Considering the balance between cytotoxicity (IC₅₀) and selectivity (SI), complex 2 was selected for mechanistic studies. Flow cytometry revealed that complex 2 effectively induced apoptosis in estrogen receptor-positive (ER+) cell lines (T47D, MCF-7), while its activity was comparatively reduced in triple-negative MDA-MB-231 cells. AO/PI co-staining and fluorescence imaging confirmed apoptotic features, including nuclear condensation and fragmentation, particularly pronounced in ER+ cells, thereby validating the cytotoxic findings. In silico ADMET predictions further indicated favorable pharmacokinetic properties, including acceptable solubility and gastrointestinal absorption. Collectively, these results establish complex 2 as a promising lead compound and highlight the importance of structural tuning in optimizing the anticancer potential of silver(I)-NHC complexes.