Microwave-Assisted Synthesis of Arene Ruthenium(II) Complex as Apoptosis Inducer of A549 Cells

Wu, Qiong; Wu, Jing; Mei, Wenjie; Wang, Qi; Zhang, Zhao; Wu, Xiaohui; Sun, Fenyong; Wu, Weili; Chen, Yan-Hua; Hu, Xiao-Ying; Tao, Yun-Yi

doi:10.1071/ch13269

Cited by 11 publications

(4 citation statements)

References 38 publications

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“…87 The Ru(II) complex acts as a groove binder to the cmyc G4 DNA forming 1:1 complex. 84 The thermodynamic feasibility (negative value of ΔG) of Pu27−TPP complex formation is also reflected in the negative MMPBSA and MMGBSA values depicted in Table 2.…”

Section: ■ Results and Discussionmentioning

confidence: 97%

“…The binding affinity obtained is comparable to previously reported literature. 14 Small molecules like sanguinarine, 82 chelerythrine, 26 diarylethynyl amides, 83 arene ruthenium(II) complexes, 84 aryl indenopyrimidine derivatives, 85 and so forth, have similar binding affinity toward c-MYC G-quadruplex structures. The molecule TPP possesses a low K d (high K a ) value but causes a modest increase in ΔT m upon binding with Pu27.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

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In Silico Screening and Binding Characterization of Small Molecules toward a G-Quadruplex Structure Formed in the Promoter Region of c-MYC Oncogene

et al. 2017

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Overexpression of c-MYC oncogene is associated with cancer pathology. Expression of c-MYC is regulated by the G-quadruplex structure formed in the G-rich segment of nuclease hypersensitive element (NHE III1), that is, “Pu27”, which is localized in the promoter region. Ligand-induced stabilization of the Pu27 structure has been identified as a novel target for cancer therapeutics. Here, we have explored the library of synthetic compounds against the predefined binding site of Pu27. Three compounds were selected based on the docking analyses; they were further scrutinized using all atom molecular dynamics simulations in an explicit water model. Simulated trajectories were scrutinized for conformational stability and ligand binding free energy estimation; essential dynamic behavior was determined using principal component analysis. One of the molecules, “TPP (1-(3-(4-(1,2,3-thiadiazol-4-yl)phenoxy)-2-hydroxypropyl)-4-carbamoylpiperidinium)”, with the best results was considered for further evaluation. The theoretical observations are supported well by biophysical analysis using circular dichroism, isothermal titration calorimetry, and high-resolution NMR spectroscopy indicating association of TPP with Pu27. The in vitro studies were then translated into c-MYC overexpression in the T47D breast cancer cell line. Biological evaluation through the MTT assay, flow cytometric assay, RT-PCR, and reporter luciferase assay suggests that TPP downregulates the expression of c-MYC oncogene by arresting its promoter region. In silico and in vitro observations cumulatively suggest that the novel skeleton of TPP could be a potential anticancer agent by stabilizing the G-quadruplex formed in the Pu27 and consequently downregulating the expression of c-MYC oncogene. Derivation of new molecules on its skeleton may confer anticancer therapeutics for the next generation.

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Section: ■ Results and Discussionmentioning

confidence: 97%

Section: ■ Results and Discussionmentioning

confidence: 99%

In Silico Screening and Binding Characterization of Small Molecules toward a G-Quadruplex Structure Formed in the Promoter Region of c-MYC Oncogene

et al. 2017

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“…10]phenanthroline, 18, Figure 5) was prepared with MAS heating of [Ru(η 6 -C 6 H 6 )Cl 2 ] 2 and o-ClPIP in dichloromethane at 60 • C for 30 min to obtain the product in higher yield (91%) than with traditional procedures [136].…”

Section: Ruthenium and Osmiummentioning

confidence: 99%

Microwave-Assisted Synthesis: Can Transition Metal Complexes Take Advantage of This “Green” Method?

Gabano

Ravera

2022

Molecules

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Microwave-assisted synthesis is considered environmental-friendly and, therefore, in agreement with the principles of green chemistry. This form of energy has been employed extensively and successfully in organic synthesis also in the case of metal-catalyzed synthetic procedures. However, it has been less widely exploited in the synthesis of metal complexes. As microwave irradiation has been proving its utility as both a time-saving procedure and an alternative way to carry on tricky transformations, its use can help inorganic chemists, too. This review focuses on the use of microwave irradiation in the preparation of transition metal complexes and organometallic compounds and also includes new, unpublished results. The syntheses of the compounds are described following the group of the periodic table to which the contained metal belongs. A general overview of the results from over 150 papers points out that microwaves can be a useful synthetic tool for inorganic chemists, reducing dramatically the reaction times with respect to traditional heating. This is often accompanied by a more limited risk of decomposition of reagents or products by an increase in yield, purity, and (sometimes) selectivity. In any case, thermal control is operative, whereas nonthermal or specific microwave effects seem to be absent.

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“…The results consistently suggest these complexes as prospective metal drugs for cancer chemotherapy. In our previous studies, arene Ru(II) complexes coordinated by phenanthroimidazole derivates displayed remarkable anti-tumor activity and low toxicity to normal cells [ 13 , 14 , 15 ]. Further investigation showed that this kind of arene Ru(II) complexes could suppress the proliferation, migration, and invasion of cancer cells by blocking the formation of invadopodia via inducing DNA damage and S-phase arrest [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

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

Qian

Liu

et al. 2022

Molecules

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A series of arene Ru(II) complexes, [(η6-MeC6H5)Ru(L)Cl]Cl, (L=o-ClPIP, 1; m-ClPIP, 2 and p-ClPIP, 3) (o-ClPIP=2-(2-chlorophenyl)imidazo[4,5-f][1,10]phenanthroline; m-ClPIP=2-(3-chlorophenyl)imidazo[4,5-f][1,10]phenanthroline; p-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 1 exhibits moderated binding affinity to KRAS G-quadruplex DNA by groove mode. Further, in vitro studies reveal that 1 displays inhibitory activity against MCF-7 growth with IC50 = 3.7 ± 0.2 μM. Flow cytometric analysis, comet assay, and immunofluorescence confirm that 1 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 KRAS G-quadruplex conformation on oncogene promoter.

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Microwave-Assisted Synthesis of Arene Ruthenium(II) Complex as Apoptosis Inducer of A549 Cells

Cited by 11 publications

References 38 publications

In Silico Screening and Binding Characterization of Small Molecules toward a G-Quadruplex Structure Formed in the Promoter Region of c-MYC Oncogene

In Silico Screening and Binding Characterization of Small Molecules toward a G-Quadruplex Structure Formed in the Promoter Region of c-MYC Oncogene

Microwave-Assisted Synthesis: Can Transition Metal Complexes Take Advantage of This “Green” Method?

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

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