Efficient synthesis of novel 1,10 phenanthroline-substituted imidazolium salts: Exploring their anticancer applications

Eur J Med Chem. 2024 Nov 5:277:116775. doi: 10.1016/j.ejmech.2024.116775. Epub 2024 Aug 13.

Abstract

This study reports a new series of 1,10-phenanthroline-substituted imidazolium salts (1a-f), examining their design, synthesis, structure and anticancer activities. The structures of these salts (1a-f) were characterized using 1H, 13C NMR, elemental analysis, mass spectrometry and Fourier transform infrared (FT-IR) spectroscopies. The salts' cytotoxic activities were tested against cancer cell lines, specifically MCF-7, MDA-MB-231 and non-tumorigenic MCF-10A mammary cells. The study compared the impact of aliphatic and benzylic groups in the salts' structure on their anticancer activity. Screening results revealed that compound 1c, in particular, showed promising inhibitory activity against the growth of MDA-MB-231 breast cancer cells, with an IC50 value of 12.8 ± 1.2 μM, indicating its potential as a chemotherapeutic agent. Cell apoptosis analysis demonstrated a tendency for compound 1c to induce early apoptosis in breast cancer cells. The stability/aquation of compound 1c was investigated using 1H NMR spectroscopy and its binding modes with DNA were explored via UV-Vis spectroscopy. Additionally, the study investigated the interaction residues and docking scores of compound 1c and the reference drug doxorubicin against Bax and Bcl-2 proteins using molecular docking.

Keywords: 1,10-Phenanthroline-imidazolium salt; Anticancer agent; Cytotoxic activity; DNA binding.

MeSH terms

  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Apoptosis* / drug effects
  • Cell Line, Tumor
  • Cell Proliferation* / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor*
  • Heterocyclic Compounds, 3-Ring / chemical synthesis
  • Heterocyclic Compounds, 3-Ring / chemistry
  • Heterocyclic Compounds, 3-Ring / pharmacology
  • Humans
  • Imidazoles* / chemical synthesis
  • Imidazoles* / chemistry
  • Imidazoles* / pharmacology
  • Molecular Docking Simulation
  • Molecular Structure
  • Phenanthrolines* / chemical synthesis
  • Phenanthrolines* / chemistry
  • Phenanthrolines* / pharmacology
  • Salts / chemical synthesis
  • Salts / chemistry
  • Salts / pharmacology
  • Structure-Activity Relationship

Substances

  • 1,10-phenanthroline
  • Antineoplastic Agents
  • Imidazoles
  • Phenanthrolines
  • Salts
  • Heterocyclic Compounds, 3-Ring