Ru(II)-Based Acetylacetonate Complexes Induce Apoptosis Selectively in Cancer Cells.
Sayak GuptaJessica M VandevordLauren M LoftusNicholas ToupinMalik H Al-AfyouniThomas N RohrabaughClaudia TurroJeremy J KodankoPublished in: Inorganic chemistry (2021)
The synthesis, chemical and biological characterization of seven Ru(II) polypyridyl complexes containing acetylacetonate (acac) ligands are reported. Electronic absorption spectra were determined and electrochemical potentials consistent with Ru(III/II) couples ranging from +0.60 to +0.73 V vs Ag/AgCl were measured. A series of complexes were screened against MDA-MB-231, DU-145, and MCF-10A cell lines to evaluate their cytotoxicities in cancer and normal cell lines. Although most complexes were either nontoxic or equipotent in cancer cells and normal cell lines, compound 1, [Ru(dpqy)(acac)(py)](PF6), where dqpy is 2,6-di(quinolin-2-yl)pyridine, showed up to 2.5:1.0 selectivity for cancer as compared to normal cells, along with nanomolar EC50 values in MDA-MB-231 cells. Lipophilicity, determined as the octanol/water partition coefficient, log Po/w, ranged from -0.33 (0.06) to 1.15 (0.10) for the complexes. Although cytotoxicity was not correlated with electrochemical potentials, a moderate linear correlation between lipophilicity and toxicities was observed. Cell death mechanism studies indicated that several of the Ru-acac compounds, including 1, induce apoptosis in MDA-MB-231 cells.
Keyphrases
- cell cycle arrest
- cell death
- pi k akt
- induced apoptosis
- endoplasmic reticulum stress
- breast cancer cells
- oxidative stress
- papillary thyroid
- signaling pathway
- energy transfer
- gold nanoparticles
- escherichia coli
- cell proliferation
- computed tomography
- staphylococcus aureus
- mass spectrometry
- molecularly imprinted
- high resolution
- molecular dynamics