Synthesis and Characterization of 1,10-Phenanthroline-Linked Imidazolium Salts: Investigation of Their Cytotoxicity Properties.

This study focuses on the synthesis, characterization, and anticancer activities of 1,10-phenanthroline-linked imidazolium salts (3) bearing different alkyl groups (methyl-(a), butyl-(b), octyl-(c), dodecyl-(d)) or benzyl (benzyl-(e), 2,4,6-trimethylbenzyl-(f)) groups. The synthesized salts were fully characterized using various analytical techniques, including UV-vis, 1H NMR, 13C NMR, FT-IR, and mass spectrometry. Their biological activities were evaluated against DU-145 (prostate cancer), MCF-7 (breast cancer), T98G (glioblastoma cancer), and the nontumorigenic HEK-293 (human embryonic kidney) cell lines. The most potent compound 3e exhibited a remarkable DNA binding constant (K b = 1.66 ± 0.1 × 106 M-1), indicating a strong interaction with DNA. Additionally, molecular docking studies were performed to assess the interaction of 3e with key apoptotic and cell cycle regulatory proteins (Bcl-2, Bcl-xL, CDK1, and Cyclin B1), suggesting a potential mechanism for its anticancer activity. ADME-related analyses of the lead compound 3e were conducted, providing an initial pharmacokinetic profile to support its progression as a preclinical candidate. In cancer cell lines, mitochondrial morphology and integrity were evaluated at IC50 concentrations against compound 3e using Invitrogen MitoTracker stain. These findings highlight the dual role of 1,10-phenanthroline-linked imidazolium salts as DNA-interacting agents and selective anticancer compounds, paving the way for their further development as targeted chemotherapeutic candidates.