Half-sandwich ruthenium(<scp>ii</scp>) complexes containing N^N-chelated imino-pyridyl ligands that are selectively toxic to cancer cells

Tian, Meng; Li, Juanjuan; Zhang, Shumiao; Guo, Lihua; He, Xiangdong; Kong, Deliang; Zhang, Hairong; Liu, Zhe

doi:10.1039/c7cc08270c

Cited by 90 publications

(66 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have reported half‐sandwich iridium complexes containing N^N‐chelating iminopyridyl ligands that displayed highly potent antiproliferative activity against cancer cells, but poor cytotoxic selectivity between cancer and normal cells . Substitution of cyclopentadienyl iridium moiety with ruthenium benzene led to a decrease of potency but better cytotoxic selectivity, suggested that the metals play a vital role in anticancer activity. Probably the ruthenium analogues of the iridium complexes in this work can achieve selectivity at some levels, which would be interesting to study in future work.…”

Section: Resultsmentioning

confidence: 99%

“…Organometallic transition metal‐based complexes exhibit a wide range of applications for the design of antitumor drugs due to their potential redox features, diverse structural types and varied ligand bonding modes . Organometallic complexes of the group VIIIB elements platinum, ruthenium, osmium, rhodium, palladium and iridium have received much attention as potential antitumor agents . Following the clinical success of platinum‐based antitumor drugs such as cisplatin, carboplatin and oxaliplatin, metal‐mediated antitumor drugs have attracted wide attention in chemotherapeutic research .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Lysosome‐targeted potent half‐sandwich iridium(III) α‐diimine antitumor complexes

Kong

Guo

Tian

et al. 2018

Applied Organom Chemis

Self Cite

View full text Add to dashboard Cite

Fifteen organometallic Ir(III) half-sandwich complexes (1A-5C) having the general formula [(η 5 -Cp x )Ir(N^N)Cl]PF 6 (Cp x = Cp*, tetramethyl(phenyl) cyclopentadienyl (Cp xph ) or tetramethyl(biphenyl)cyclopentadienyl (Cp xbiph ); N^N = diamine) have been synthesized and characterized. The molecular structure of 1A was determined using single-crystal X-ray diffraction analysis.The hydrolysis of 1A-5C was monitored using UV-visible spectra. Complexes 3A-3C showed catalytic activity for the oxidation of NADH to NAD + , where 3C showed the highest turnover number of 29.9 within 450 min. Cytotoxicity examination by MTT assay was carried out against two human cancer cell lines (HeLa and A549) after 24 or 48 h drug treatment. The complexes showed high potency, where the most potent complex (3C; IC 50 = 3.4 μM) was six times more active than cisplatin against A549 cells after 24 h drug exposure. Cytotoxic potency towards A549 cells increased with phenyl substitution on Cp ring: Cp xbiph > Cp xph > Cp*. In addition, the biological studies showed that 3C caused cell apoptosis and cell cycle arrest at G 1 phase in A549 cancer cells.Moreover, 3C increased the level of reactive oxygen species markedly after 24 h, which may provide an important basis for killing cancer cells. Confocal laser scanning microscopy was used to track 3C in A549 cells. The cellular localization experiment showed that 3C targeted lysosomes and caused lysosomal damage.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lysosome‐targeted potent half‐sandwich iridium(III) α‐diimine antitumor complexes

Kong

Guo

Tian

et al. 2018

Applied Organom Chemis

Self Cite

View full text Add to dashboard Cite

show abstract

“…The interaction of base pairs of DNA with complexes usually involves intercalation, interaction, non-intercalative electrostatic interactions as wella sd amage of the DNA double helix. [42][43][44][45] The change in the absorption wavelength of the as-synthesized complexes as the amount of CT-DNA (DNA sodium from calf thymus) increased was determined by means of UV/Vis titration, and the bindingc onstants( K b )o ft he complexes were also calculated. The role of metal iridium in our complexes is probablyt op rovideacoordination center.…”

Section: Interaction With Ct-dnamentioning

confidence: 99%

Triphenylamine‐Appended Half‐Sandwich Iridium(III) Complexes and Their Biological Applications

Tian

Liu

et al. 2018

Chemistry An Asian Journal

Self Cite

View full text Add to dashboard Cite

Organometallic half-sandwich Ir complexes of the type [(η -Cp )Ir(N^N)Cl]PF (Cp : Cp* or its phenyl Cp or biphenyl Cp derivatives; N^N: triphenylamine (TPA)-substituted bipyridyl ligand groups) were synthesized and characterized. The complexes showed excellent bovine serum albumin (BSA) and DNA binding properties and were able to oxidize NADH to NAD (NAD=nicotinamide adenine dinucleotide) efficiently. The complexes induced apoptosis effectively and led to the emergence of reactive oxygen species (ROS) in cells. All complexes showed potent cytotoxicity with IC values ranging from 1.5 to 7.1 μm toward A549 human lung cancer cells after 24 hours of drug exposure, which is up to 14 times more potent than cisplatin under the same conditions.

show abstract

“…However, similar to other cytotoxic drugs, problems of platinum‐based anticancer drugs, normal tissue toxicity, and drug resistance limit their future use . These factors necessitate the exploration of new chemotype anticancer agents that have metal and new mechanisms of action different from platinum …”

Section: Introductionmentioning

confidence: 99%

Dual Functional Half‐Sandwich Ru(II) Complexes: Lysosome‐Targeting Probes and Anticancer Agents

Liu

Kong

et al. 2019

Eur J Inorg Chem

Self Cite

View full text Add to dashboard Cite

It is known that the proposed biologically active form of ruthenium is its oxidation state II other than oxidation state III, and ruthenium complexes offer the potential of a novel mechanism of action, reduced toxicity. Herein, three half‐sandwich RuII complexes [(η6‐p‐cym)Ru(N^N)Cl]PF6 were designed and synthesized. Lysosomes are involved in various aspects of cancer cell immortalization and cell death. Thus, lysosomes are attractive pharmacological targets for selective killing of cancer cells. We demonstrated that Ru2 can accumulate in lysosomes. In addition, A549 cell viability remained at 87.81 % after exposure to Ru2 for 24 h at the working concentration. Meanwhile, Ru2 exhibited relatively high photostability and suitability for long‐term tracking. At increased concentration after 24 h of exposure to the complex toward A549 cell line, Ru2 induced a high apoptotic rate, cell cycle arrest, mitochondrial membrane potential loss, and reactive oxygen species overload. Ru2 integrated the anticancer properties and imaging capabilities and is expected to be developed as a dual functional theranostic agent.

show abstract

Half-sandwich ruthenium(ii) complexes containing N^N-chelated imino-pyridyl ligands that are selectively toxic to cancer cells

Cited by 90 publications

References 22 publications

Lysosome‐targeted potent half‐sandwich iridium(III) α‐diimine antitumor complexes

Lysosome‐targeted potent half‐sandwich iridium(III) α‐diimine antitumor complexes

Triphenylamine‐Appended Half‐Sandwich Iridium(III) Complexes and Their Biological Applications

Dual Functional Half‐Sandwich Ru(II) Complexes: Lysosome‐Targeting Probes and Anticancer Agents

Contact Info

Product

Resources

About