Curcumin and cyclopalladated complexes: A recipe for bifunctional biomaterials

Pucci, Daniela; Bloise, Rossana; Bellusci, Anna; Bernardini, Sergio; Ghedini, Mauro; Pirillo, Sante; Valentini, Alessandra; Crispini, Alessandra

doi:10.1016/j.jinorgbio.2007.03.006

Cited by 42 publications

(26 citation statements)

References 35 publications

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“…The following reagents were used: a heteroleptic pentacoordinated (bpy-9)Zn(curc, Cl) complex containing a 4,4′-disubstituted-2,2′-bipyridine as main ligand and curcumin (curc) and chloride (Cl) as ancillary ligands [13] was dissolved in DMSO and used at the indicated concentrations; curcumin was prepared as previously reported [17]; pifithryn-α (PFT-α) (ENZO Life Sciences, Lausen Switzerland) was dissolved in DMSO and used at 30 μM; adryamycin (ADR) was used at 2 μg/ml and ZnCl 2 was used at 100 μM.…”

Section: Methodsmentioning

confidence: 99%

A fluorescent curcumin-based Zn(II)-complex reactivates mutant (R175H and R273H) p53 in cancer cells

Garufi

Trisciuoglio

Porru

et al. 2013

J Exp Clin Cancer Res

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BackgroundMutations of the p53 oncosuppressor gene are amongst the most frequent aberration seen in human cancer. Some mutant (mt) p53 proteins are prone to loss of Zn(II) ion that is bound to the wild-type (wt) core, promoting protein aggregation and therefore unfolding. Misfolded p53 protein conformation impairs wtp53-DNA binding and transactivation activities, favouring tumor growth and resistance to antitumor therapies. Screening studies, devoted to identify small molecules that reactivate mtp53, represent therefore an attractive anti-cancer therapeutic strategy. Here we tested a novel fluorescent curcumin-based Zn(II)-complex (Zn-curc) to evaluate its effect on mtp53 reactivation in cancer cells.MethodsP53 protein conformation was examined after Zn-curc treatment by immunoprecipitation and immunofluorescence assays, using conformation-specific antibodies. The mtp53 reactivation was evaluated by chromatin-immunoprecipitation (ChIP) and semi-quantitative RT-PCR analyses of wild-type p53 target genes. The intratumoral Zn-curc localization was evaluated by immunofluorescence analysis of glioblastoma tissues of an ortothopic mice model.ResultsThe Zn-curc complex induced conformational change in p53-R175H and -R273H mutant proteins, two of the most common p53 mutations. Zn-curc treatment restored wtp53-DNA binding and transactivation functions and induced apoptotic cell death. In vivo studies showed that the Zn-curc complex reached glioblastoma tissues of an ortothopic mice model, highlighting its ability to crossed the blood-tumor barrier.ConclusionsOur results demonstrate that Zn-curc complex may reactivate specific mtp53 proteins and that may cross the blood-tumor barrier, becoming a promising compound for the development of drugs to halt tumor growth.

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Section: Methodsmentioning

confidence: 99%

A fluorescent curcumin-based Zn(II)-complex reactivates mutant (R175H and R273H) p53 in cancer cells

Garufi

Trisciuoglio

Porru

et al. 2013

J Exp Clin Cancer Res

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“…118 Finally, Aldrich-Wright and co-workers reported a simple and mild synthetic protocol for obtaining cationic palladacyclic complexes (Fig. Further studies were performed on complex 41 to understand the mechanism of cell growth inhibition and cell death through mitochondrial bearing membrane depolarization.…”

Section: View Article Onlinementioning

confidence: 99%

Anti-cancer palladium complexes: a focus on PdX₂L₂, palladacycles and related complexes

2014

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Much success has been achieved with platinum-based chemotherapeutic agents, i.e. through interactions with DNA. The long-term application of Pt complexes is thwarted by issues, leading scientists to examine other metals such as palladium which could exhibit complementary modes of action (given emphasis wherever known). Over the last 10 years several research groups have focused on the application of an eclectic array of palladium complexes (of the type PdX2L2, palladacycles and related structures) as potential anti-cancer agents. This review therefore provides readers with an up to date account of the advances that have taken place over the past several decades.

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“…on cytotoxic orthometallated palladium complexes 22 (some containing thiosemicarbazone ligands) a few cyclopalladated compounds with potential anticancer activities have been described. 23-25 The higher stability of cyclopalladated compounds in physiological media together with a lower toxicity to normal cells are promising features for their biological applications. 18b Biphosphinic palladacycles of the type [Pd(C 2 ,N-(S (-) dmap)(dppf)]Cl induced apoptotic cell death in human leukemia cells by rupture of lysosomal membrane and release of cathepsin B in the cytoplasm.…”

Section: Introductionmentioning

confidence: 99%

Organometallic Palladium Complexes with a Water-Soluble Iminophosphorane Ligand As Potential Anticancer Agents

et al. 2012

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The synthesis and characterization of a new water-soluble iminophosphorane ligand TPAN-C(O)-2BrC6H4 (1, C,N-IM; TPA = 1,3,5-triaza-7-phosphaadamantane) is reported. Oxidative addition of 1 to Pd2(dba)3 affords the orthopalladated dimer [Pd(μ-Br){C6H4(C(O)NTPA-kC,N)-2}]2 (2) as a mixture of cis and trans isomers (1:1 molar ratio) where the iminophosphorane moeity behaves as a C,N-pincer ligand. By addition of different neutral or monoanionic ligands to 2, the bridging chlorides can be cleaved and a variety of hydrophilic or water-soluble mononuclear organometallic palladium(II) complexes of the type [Pd{C6H4(C(O)NTPA-kC,N)-2}(L-L)] (L-L = acac (3); S2CNMe2 (4); 4,7-diphenyl-1,10-phenanthrolinedisulfonic acid disodium salt C12H6N2(C6H4SO3Na)2 (5)), [Pd{C6H4(C(O)NTPA-kC,N)-2}(L)Br] (L = P(mC6H4SO3Na)3 (6); P(3-pyridyl)3 (7)), and [Pd(C6H4(C(O)NTPA)-2}(TPA)2Br] (8) are obtained as single isomers. All new complexes were tested as potential anticancer agents, and their cytotoxicity properties were evaluated in vitro against human Jurkat-T acute lymphoblastic leukemia cells, normal T-lymphocytes (PBMC), and DU-145 human prostate cancer cells. Compounds [Pd(μ-Br){C6H4(C(O)NTPA-kC,N)-2}]2 (2) and [Pd{C6H4(C(O)NTPA-kC,N)-2}(acac)] (3) (which has been crystallographically characterized) display higher cytotoxicity against the above-mentioned cancer cell lines while being less toxic to normal T-lymphocytes (peripheral blood mononuclear cells: PBMC). In addition, 3 is very toxic to cisplatin-resistant Jurkat shBak, indicating a cell death pathway that may be different from that of cisplatin. The interaction of 2 and 3 with plasmid (pBR322) DNA is much weaker than that of cisplatin, pointing to an alternative biomolecular target for these cytotoxic compounds. All the compounds show an interaction with human serum albumin faster than that of cisplatin.

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Curcumin and cyclopalladated complexes: A recipe for bifunctional biomaterials

Cited by 42 publications

References 35 publications

A fluorescent curcumin-based Zn(II)-complex reactivates mutant (R175H and R273H) p53 in cancer cells

A fluorescent curcumin-based Zn(II)-complex reactivates mutant (R175H and R273H) p53 in cancer cells

Anti-cancer palladium complexes: a focus on PdX₂L₂, palladacycles and related complexes

Organometallic Palladium Complexes with a Water-Soluble Iminophosphorane Ligand As Potential Anticancer Agents

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Curcumin and cyclopalladated complexes: A recipe for bifunctional biomaterials

Cited by 42 publications

References 35 publications

A fluorescent curcumin-based Zn(II)-complex reactivates mutant (R175H and R273H) p53 in cancer cells

A fluorescent curcumin-based Zn(II)-complex reactivates mutant (R175H and R273H) p53 in cancer cells

Anti-cancer palladium complexes: a focus on PdX2L2, palladacycles and related complexes

Organometallic Palladium Complexes with a Water-Soluble Iminophosphorane Ligand As Potential Anticancer Agents

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Anti-cancer palladium complexes: a focus on PdX₂L₂, palladacycles and related complexes