Ruthenium(II) arene complexes bearing 1,10-phenanthroline substituted with an imidazolium salt: Synthesis, and cytotoxic activities


Çakır S., ATMACA İLHAN H., İLHAN M. S., Türkmen H.

Journal of Inorganic Biochemistry, cilt.270, 2025 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 270
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1016/j.jinorgbio.2025.112937
  • Dergi Adı: Journal of Inorganic Biochemistry
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, Chimica, Veterinary Science Database
  • Anahtar Kelimeler: 1,10-phenanthroline-substituted imidazolium salts, Cell cycle analysis, Cytotoxicity, DNA/BSA binding studies, Molecular docking, Ruthenium(II) arene complex
  • Manisa Celal Bayar Üniversitesi Adresli: Evet

Özet

Researchers are increasingly focusing on developing target-specific, highly cytoselective, lipophilic, water-soluble Ru(II) arene complexes to mitigate the side effects of commercially available platinum-based anticancer drugs. In this context, we present novel Ru(II) arene complexes, (Ru1 and Ru1a-f), which are based on a 1,10-phenanthroline-substituted imidazolium core derivatized with alkyl (butyl(a), octyl(b), dodecyl(c)) or benzyl ((benzyl(d), 2,4,6-trimethylbenzyl(e), pentamethylbenzyl(f)) groups. The structures of these complexes were characterized using 1H, 13C, 19F and, 31P nuclear magnetic resonance (NMR) spectroscopy, Fourier transform infrared spectroscopy, mass spectrometry and elemental analysis. The cytotoxic activities of Ru1 and Ru1a-f complexes were tested against the cancer cell lines MCF-7 and MDA-MB-231 and normal cell lines, such as MCF-10 A. The cell cycle distribution in the MCF-7 and MDA-MB-231 breast cancer cell lines after 72 h of incubation with IC50 concentration of the complex Ru1c can validly inhibit cell growth in the G2/M phase. Flow cytometry analysis showed that the complex Ru1c induced apoptosis in MCF-7 and MDA-MB-231 breast cancer cells. Additionally, the binding mode of the complex Ru1c with Fish-Salmon DNA was examined using ultraviolet-visible spectroscopy. Interaction of Ru1c complex with bovine serum albumin was analyzed by absorption study. The stability of all complexes in the solvent was assessed using 1H NMR spectroscopy. Additionally, quantitative determination of the total ruthenium level within the cells was performed by inductively coupled plasma mass spectrometry (ICP-MS). Molecular docking was performed to evaluate the interaction residues and docking scores of Ru1c and the reference drug cis‑platinum against CDK1, cyclin B1, Bcl-xL and Bcl-2 proteins.