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- Title
Mononuclear η<sup>6</sup>-arene ruthenium(II) complexes with pyrazolyl–pyridazine ligands: synthesis, CT-DNA binding, reactivity towards glutathione, and cytotoxicity.
- Authors
Kanyora, Amos K.; Omondi, Reinner O.; Ongoma, Peter; Omolo, Josiah O.; Welsh, Athi; Prince, Sharon; Gichumbi, Joel; Mambanda, Allen; Smith, Gregory S.
- Abstract
Organometallic η6-arene ruthenium(II) complexes with 3-chloro-6-(1H-pyrazol-1-yl)pyridazine (Ru1, Ru2, and Ru5) and 3-chloro-6-(3,5-dimethyl-1H-pyrazol-1-yl)pyridazine (Ru3-4) N,N' heterocyclic and η6-arene (cymene (Ru1-4) or toluene (Ru 5)) have been synthesized. The ruthenium(II) complexes have common "three-legged piano-stool" pseudo-octahedral structures known for half-sandwich complexes. Evolution of their UV–Visible absorption spectra in PBS buffer or DMSO over 24 h confirmed their good solvolysis stability. Titrations of the complexes with the calf thymus DNA (CT-DNA) were monitored using UV–Visible absorption and fluorescence spectroscopies. The complexes interact moderately with CT-DNA and their binding constants are in the order of 104 M−1. Competitive binding of the complexes to a DNA-Hoechst 33,258 depicted competitive displacement of Hoechst from DNA's minor grooves. These complexes bind to glutathione forming GSH-adducts through S coordination by replacement of a halide, with the iodo-analogues having higher binding constants than the chloro-complexes. Cyclic voltammograms of the complexes exhibited one electron-transfer quasi-reversible process. Trends in the molecular docking data of Ru1-5/DNA were similar to those for DNA binding constants. Of the five, only Ru1, Ru3 and Ru5 showed some activity (moderate) against the MCF-7 breast cancer cells with IC50 values in the range of 59.2–39.9 for which Ru5 was the most active. However, the more difficult-to-treat cell line, MDA-MB 231 cell was recalcitrant to the treatment by these complexes. Molecular docking simulations visualized the interactions of arene Ru(II) complexes with CT-DNA via minor grooving. The trends were corroborated by electrochemical and cytotoxicity data.
- Subjects
CYTOTOXINS; RUTHENIUM; GLUTATHIONE; BINDING constant; MOLECULAR docking; SCHIFF bases; RUTHENIUM compounds; PYRIDAZINES
- Publication
Journal of Biological Inorganic Chemistry (JBIC), 2024, Vol 29, Issue 2, p251
- ISSN
0949-8257
- Publication type
Article
- DOI
10.1007/s00775-024-02043-3