A synthetic dinuclear copper(II) hydrolase and its potential as antitumoral: Cytotoxicity, cellular uptake, and DNA cleavage

Rey, Nicolás A.; Neves, Ademir; Silva, Priscila P.; Paula, Flávia C. S. de; Silveira, Josianne Nicácio; Botelho, Françoise Vasconcelos; Vieira, Leda Quércia; Pich, Claus Tröger; Terenzi, Hernán; Pereira-Maia, Elene C.

doi:10.1016/j.jinorgbio.2009.05.008

Cited by 50 publications

(32 citation statements)

References 37 publications

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“…The in vitro assay of the nuclease activity uses supercoiled plasmid DNA (FI) as a substrate. Single-strand cleavage by CCS results in an open circular DNA (FII), while cleavage involving two DNA strands results in the linear form (FIII) (Rey et al, 2009). Decreased FI and concomitant intensification of FII and FIII forms indicates a dose-dependent cleavage of plasmid DNA by CCS at 0.78-3.12 mg/mL.…”

Section: Resultsmentioning

confidence: 99%

“…This DNA interaction may involve intercalation between base pairs, and cleavage of the DNA molecule, and may be a significant antitumor mechanism of new compounds (Rey et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

“…One of the main problems with currently available anticancer drugs is their non-selective cytotoxicity, which leads to various adverse effects. In addition, the development of multi-drug resistant cancer cells often restricts successful therapeutic outcomes (Rey et al, 2009). In recent years, much research has been devoted to the discovery of novel cost-effective anticancer agents with minimal side effects from natural products.…”

Section: Introductionmentioning

confidence: 99%

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Anticancer activity of flavonol and flavan-3-ol rich extracts fromCroton celtidifoliuslatex

Biscaro

Parisotto

Zanette

et al. 2013

Pharmaceutical Biology

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Context: Croton celtidifolius Baill (Euphorbiaceae) is a tree found in the Atlantic Forest in Southern Brazil, where it is commonly known as ''Sangue-de-Dragão''. Its red latex is used traditionally for treating ulcers, diabetes and cancer. Objective: To evaluate antitumor activities of Croton celtififolius latex in vitro and in vivo. Material and methods: Phytochemical analyses were conducted using HPLC-DAD-MS. Cytotoxic, nuclease and pro-apoptotic properties were determined using the tetrazolium salt assay (MTT), plasmid DNA damage assay and ethidium bromide (EB)/acridine orange methods, respectively, and antitumor activity was determined in the Ehrlich ascites carcinoma (EAC) mouse model. Results: Phytochemical studies indicated a high phenol content of flavonols (45.67 AE 0.24 and 18.01 AE 0.23 mg/mL of myricetin and quercetin, respectively) and flavan-3-ols (114.12 AE 1.84 and 1527.41 AE 16.42 mg/L of epicatechin and epigallocatechin, respectively) in latex. These compounds reduced MCF-7 and EAC cell viability in the MTT assay (IC 50 ¼ 169.0 AE 1.8 and 187.0 AE 2.2 mg/mL, respectively). Latex compounds caused significant DNA fragmentation and increased the number of apoptotic cells (negative control (NC), 12%; latex, 41%) as indicated by differential staining in the EB/acridine orange assay. The in vivo latex treatment at 3.12 mg/kg/day reduced the body weight by 7.57 AE 2.04 g and increased median survival time to 17.5 days when compared to the NC group (13.0 days). In addition, the highest latex concentration inhibited tumor growth by 56%. Discussion and conclusion: These results agree with ethno-pharmacological reports showing cytotoxicity and antitumor activity of C. celtidifolius latex. The mechanism of antitumor action may be related to direct DNA fragmentation that reduces survival and induces apoptosis.

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Section: Resultsmentioning

confidence: 99%

“…This DNA interaction may involve intercalation between base pairs, and cleavage of the DNA molecule, and may be a significant antitumor mechanism of new compounds (Rey et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Anticancer activity of flavonol and flavan-3-ol rich extracts fromCroton celtidifoliuslatex

Biscaro

Parisotto

Zanette

et al. 2013

Pharmaceutical Biology

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“…Also, the cytotoxicity efficiency of the Cr(III) and Ru(III) complexes is comparable with that of the standard drug, cis-platin, while the Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) complexes showed lower anticancer activities when compared to that of the ligand. The cytotoxicity of metal complexes is depending on their ability to bind DNA and damage its structure resulting in the impairment of its function, which is followed by replication and transcription processes inhibition and eventually cell death that is what we can suppose [22][23][24][25][26]. Thus, the relatively higher cytotoxicity exhibited by the Cr(III) and Ru(III) complexes may be due to the relatively stronger binding ability of the complexes with DNA as shown in the DNA binding studies.…”

Section: Structure Of the Complexesmentioning

confidence: 99%

Synthesis, Spectral Characterization, and Thermal and Cytotoxicity Studies of Cr(III), Ru(III), Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) Complexes of Schiff Base Derived from 5-Hydroxymethylfuran-2-carbaldehyde

Alturiqi

Alaghaz

Ammar

et al. 2018

Journal of Chemistry

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Coordination compounds of Cr(III), Ru(III), Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) ions were synthesized from the furan ligand [5-hydroxymethylfuran-2-yl-methyleneaminoquinolin-2-one] (H-MFMAQ) derived from the condensation of 5-hydroxymethylfuran-2-carbaldehyde and 1-aminoquinolin-2(1H)-one. Elemental analytical data, IR, NMR ( 1 H, 13 C, and 15 N), EPR, XRD, SEM, TEM, EDX, TGA, mass, molar conductance, magnetic moment, and UV-Visible spectra techniques were used to confirm the structure of the synthesized chelates. According to the data obtained, the composition of the 1 : 1 metal ions : furan Schiff base ligand was found to be [M(MFMAQ)Cl 2 ] (M = Cr(III) and Ru(III)) and [M(MFMAQ)Cl(H 2 O)]⋅nH 2 O in which (M = Mn(II); = 1, Co(II); = 0, Ni(II); = 2, Cu(II); = 0 and Zn(II); = 2.5). The measurements of magnetic susceptibility, ligand field parameter, and reflectance spectra suggested an octahedral geometry for the complexes. Central metals ions and furan Schiff base coordinated via O3 and N donor sites which was observed from IR spectra. The cytotoxic activities of all inspected compounds were evaluated towards human breast (MCF-7) and lung cancer (A549) cell lines.

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“…This is corroborated by the absence of NC form increase, indicating that the cleavage occurs through double-strand breaks instead of single strand. Thus, one might consider that ZM5 shows the capability to promote double-strand breaks [29][30][31][32]. We then evalu- It is often accepted that Cu(II) complexes are capable to cleave DNA by hydrolytic mechanisms, but these compounds have also been reported to generate ROS in presence of a reductant and dioxygen to induce oxidative cleavage of DNA [26,33].…”

Section: Effect Of Zm5 On Dnamentioning

confidence: 99%

Characterization of antiproliferative potential and biological targets of a copper compound containing 4′-phenyl terpyridine

et al. 2015

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Several copper complexes have been assessed as anti-tumor agents against cancer cells. In this work, a copper compound [Cu(H2O){OS(CH3)2}L](NO3)2 incorporating the ligand 4'-phenyl-terpyridine antiproliferative activity against human colorectal, hepatocellular carcinomas and breast adenocarcinoma cell lines was determined, demonstrating high cytotoxicity. The compound is able to induce apoptosis and a slight delay in cancer cell cycle progression, probably by its interaction with DNA and induction of double-strand pDNA cleavage, which is enhanced by oxidative mechanisms. Moreover, proteomic studies indicate that the compound induces alterations in proteins involved in cytoskeleton maintenance, cell cycle progression and apoptosis, corroborating its antiproliferative potential.

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A synthetic dinuclear copper(II) hydrolase and its potential as antitumoral: Cytotoxicity, cellular uptake, and DNA cleavage

Cited by 50 publications

References 37 publications

Anticancer activity of flavonol and flavan-3-ol rich extracts fromCroton celtidifoliuslatex

Anticancer activity of flavonol and flavan-3-ol rich extracts fromCroton celtidifoliuslatex

Synthesis, Spectral Characterization, and Thermal and Cytotoxicity Studies of Cr(III), Ru(III), Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) Complexes of Schiff Base Derived from 5-Hydroxymethylfuran-2-carbaldehyde

Characterization of antiproliferative potential and biological targets of a copper compound containing 4′-phenyl terpyridine

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