Arene Ru(II) Complexes Acted as Potential KRAS G-Quadruplex DNA Stabilizer Induced DNA Damage Mediated Apoptosis to Inhibit Breast Cancer Progress

A series of arene Ru(II) complexes, [( -MeC H )Ru(L)Cl]Cl, (L= -ClPIP, ; -ClPIP, and -ClPIP, ) ( -ClPIP=2-(2-chlorophenyl)imidazo[4,5-f][1,10]phenanthroline; -ClPIP=2-(3-chlorophenyl)imidazo[4,5-f][1,10]phenanthroline; -ClPIP=2-(4-chlorophenyl)imidazo[4,5-f][1,10]phenanthroline) was synthesized and...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2022-05, Vol.27 (10), p.3046
Main Authors: Qian, Jiayi, Liu, Ruotong, Liu, Ningzhi, Yuan, Chanling, Wu, Qiong, Chen, Yanhua, Tan, Weijun, Mei, Wenjie
Format: Article
Language:English
Subjects:
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Apoptosis
arene ruthenium complex
Binding
Breast cancer
Breast Neoplasms - drug therapy
Cell cycle
Chemotherapy
Comet assay
Conformation
Deoxyribonucleic acid
DNA
DNA Damage
Female
Flow cytometry
G-Quadruplexes
G1 phase
Grooves
Humans
Immunofluorescence
K-Ras protein
KRAS G-quadruplex DNA
Ligands
Molecular docking
Molecular Docking Simulation
Phenanthrolines - chemistry
Proto-Oncogene Proteins p21(ras) - genetics
Ruthenium - chemistry
Ruthenium - pharmacology
Spectroscopy
Spectrum analysis
Toxicity
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Summary:A series of arene Ru(II) complexes, [( -MeC H )Ru(L)Cl]Cl, (L= -ClPIP, ; -ClPIP, and -ClPIP, ) ( -ClPIP=2-(2-chlorophenyl)imidazo[4,5-f][1,10]phenanthroline; -ClPIP=2-(3-chlorophenyl)imidazo[4,5-f][1,10]phenanthroline; -ClPIP=2-(4-chlorophenyl)imidazo[4,5-f][1,10]phenanthroline) was synthesized and investigated as a potential apoptosis inducer in chemotherapy. Spectroscopy and molecular docking simulations show that exhibits moderated binding affinity to G-quadruplex DNA by groove mode. Further, in vitro studies reveal that displays inhibitory activity against MCF-7 growth with IC = 3.7 ± 0.2 μM. Flow cytometric analysis, comet assay, and immunofluorescence confirm that can induce the apoptosis of MCF-7 cells and G0/G1 phase arrest through DNA damage. In summary, the prepared arene Ru(II) complexes can be developed as a promising candidate for targeting G-quadruplex structure to induce the apoptosis of breast cancer cells via binding and stabilizing G-quadruplex conformation on oncogene promoter.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules27103046