Platinum Intercalators of DNA as Anticancer Agents

Pages, Benjamin J.; Garbutcheon‐Singh, K. Benjamin; Aldrich‐Wright, Janice R.

doi:10.1002/ejic.201601204

Cited by 43 publications

(21 citation statements)

References 87 publications

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“…Owing to the numerous side effects, long‐term resistance and clinical limitations of the well‐known first‐generation Pt(II) anticancer complex cisplatin (Chart 1a), numerous DNA‐binding platinum drugs have been developed over the years . The so‐called second‐generation platinum drugs include Pt(II) complexes which deviate from the cisplatin template as the metal centre experiences a different ligand field, leading to a modulation of the electronic, steric hindrance and basicity features .…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic performances of new anionic cyclometalated Pt(II) complexes bearing chelated O^O ligands

Ionescu

Caligiuri

Godbert

et al. 2020

Applied Organom Chemis

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The in vitro biological activity towards the MDA‐MB‐231 triple‐negative breast cancer cell line of two different series of anionic Pt(II) organometallic complexes was tested. For the first time, cytotoxic activity of anionic Pt(II) complexes has been observed. The anionic compounds of general formula NBu4[(C^N)Pt(O^O)], where (C^N) represents the cyclometalated form of 2‐phenylpyridine (H(PhPy)), 2‐thienylpyridine (H(Thpy)) or 2‐benzo[h]quinoline (H(Bzq)), feature two different (O^O) chelated ligands: tetrabromocatechol [BrCat]2− (1–3) or alizarine [Aliz]2− (4–6). Complexes 1–6 displayed a significant cytotoxic effect against the studied cell line (IC50 range of 1.9–52.8 μM). For BrCat‐containing complexes 1–3, the biological activity was independent of the nature of the coordinated (C^N) ligand. In contrast, in the case of 4–6, the cytotoxicity (significantly high for 4) was concomitantly induced by the presence of either the PhPy or the [Aliz]2− ligand. Since complexes 1–6 are emissive in solution, the potential use of 4 as a theranostic agent was investigated using confocal analysis. The fluorescence signal from MDA‐MB‐231 cells incubated with 4 indicated the localization of the compound into the cytosol region.

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Section: Introductionmentioning

confidence: 99%

Cytotoxic performances of new anionic cyclometalated Pt(II) complexes bearing chelated O^O ligands

Ionescu

Caligiuri

Godbert

et al. 2020

Applied Organom Chemis

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“…[42,43] Many Pt(II) complexes have proved as good intercalators causing space between its base pairs by unwinding of DNA helix, which makes them potential mutagens. [44] Our previous work about dinuclear Pt(II) complexes with 1,5-naphthyridine (1,5-nphe) as a bridging ligand showed that these complexes have tendency to bind to negative charging DNA backbone. [23] Coordinated ligands also play an important role in the binding of platinum(II) complexes to DNA, so multiple modes of DNA binding can be achieved by changing different ligands.…”

Section: Spectroscopic Characterizationmentioning

confidence: 99%

Synthesis, DNA‐/bovine serum albumin‐binding affinity, and cytotoxicity of dinuclear platinum(II) complexes with 1,6‐naphthyridine‐bridging ligand

Konovalov

Franich

Jurišević

et al. 2020

Applied Organom Chemis

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The dinuclear platinum(II) complexes, [{PtCl(NH 3) 2 } 2 (μ-1,6-nphe)](ClO 4) 2 (Pt1) and [{Pt(en)Cl} 2 (μ-1,6-nphe)](ClO 4) 2 (Pt2) (en is a bidentate-coordinated ethylenediamine and 1,6-nphe is the bridging 1,6-naphthyridine ligand) were synthesized and characterized by different spectroscopic methods. The DNAbinding evaluation of complexes Pt1 and Pt2 was done by UV-Vis, fluorescence emission spectroscopy, and their interaction with bovine serum albumin (BSA). The cytotoxic activity of these complexes was determined against mouse breast (4T1) and colon (CT26) cancer cell lines, human breast (MDA-MB-468), colon (HCT-116), and lung (A549) cancer cell lines as well as mouse mesenchymal stem cells (mMSC). Complex Pt1 showed higher cytotoxic capacity toward solid cancer cell lines compared with Pt2 and lower cytotoxic capacity toward mMSC cells compared with cisplatin. Furthermore, molecular mechanism studies showed that Pt1 complex induced 4T1 and A549 cell apoptosis therefore increasing expression of pro-apoptotic caspase-3 and decreasing expression of anti-apoptotic Bcl-2 and Ki-67. Antitumor capacity of Pt1 complex might be manifested at least in two ways: by facilitating apoptosis and by inhibiting tumor cells proliferation.

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“…The resulting compound, 4, had a characteristic red colour due to the charge transfer band that is present also in complex 2 (Supplementary Info) and was fully characterised by NMR and mass spectrometry. The DTPA backbone resonances agree with the pattern of compound 3, while 1 H-1 H correlation spectroscopy (COSY) was employed to reveal the couplings of the overlapping protons in the aromatic region.…”

Section: Synthesis and Characterisationmentioning

confidence: 99%

“…Polymetallic nanostructures bring novel, distinct, recognition features to their interaction with nucleic acids, which govern the sensing function in diagnostic assays and their application in photodynamic therapy. [1][2][3][4][5][6][7][8][9][10][11] The effect of bis-intercalator units on the structural changes to DNA is of particular interest because the tethering of the two intercalators affects the DNA-binding and this can also influence the biological activity. [12][13][14][15][16][17][18][19][20] We have previously introduced the bisamide of diethylene triamine pentaacetic acid (DTPA) as a scaffold for the attachment of platinum units to form DNA bis-intercalators [20] in order to introduce a luminescent lanthanide site "remote" from the intercalating unit.…”

Section: Introductionmentioning

confidence: 99%

A luminescent europium hairpin for DNA photosensing in the visible, based on trimetallic bis-intercalators

Scarpantonio

Cotton

Giorgio

et al. 2020

Journal of Inorganic Biochemistry

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Platinum Intercalators of DNA as Anticancer Agents

Cited by 43 publications

References 87 publications

Cytotoxic performances of new anionic cyclometalated Pt(II) complexes bearing chelated O^O ligands

Cytotoxic performances of new anionic cyclometalated Pt(II) complexes bearing chelated O^O ligands

Synthesis, DNA‐/bovine serum albumin‐binding affinity, and cytotoxicity of dinuclear platinum(II) complexes with 1,6‐naphthyridine‐bridging ligand

A luminescent europium hairpin for DNA photosensing in the visible, based on trimetallic bis-intercalators

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