Cytotoxic activity of proflavine diureas: Synthesis, antitumor, evaluation and DNA binding properties of 1′,1″-(acridin-3,6-diyl)-3′,3″-dialkyldiureas

Kožurková, Mária; Sabolová, Danica; Janovec, Ladislav; Mikeš, Jaromír; Kovaľ, Ján; Ungvarsky, Jan; Štefanišinová, Miroslava; Fedoročko, Peter; Kristián, Pavol; Imrich, Ján

doi:10.1016/j.bmc.2008.01.026

Cited by 60 publications

(44 citation statements)

References 19 publications

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“…The spectrum recorded slight bathochromic and profound hypochromic effects by the addition of DNA. These observations are attributable to the intercalation of DSP with DNA 10 . The UV-Vis spectrum ( Figure. 3) of the drug showed a 3 nm red shift from 243 nm to 246 nm, accompanied with a 37.4% decrease in absorbance of the initial value.…”

Section: Reagentsmentioning

confidence: 79%

Thermodynamic Characterization of Dexamethasone Sodium Phosphate and Its Complex With Dna as Studied by Conductometric and Spectroscopic Techniques

Shah

Khan

Usman

et al. 2009

J. Chil. Chem. Soc.

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Electrical conductivities were measured to calculate critical aggregation concentration (cac) of dexamethasone sodium phosphate (DSP) at various temperature from 298-313K with an increment of 5 K and in this way its thermodynamic parameters like Gibbs energy of aggregation (°∆ agg G ) , enthalpy of aggregation (°∆ agg H ) and entropy of aggregation (°∆ agg S ) were estimated. The results demonstrate that DSP forms enthalpy driven aggregates through open association process. Furthermore, its interaction with DNA was studied by UV-Vis spectroscopy. The binding constant of DSP-DNA interaction was evaluated at 298 K and 310 K. Gibbs energy of drug-DNA complexation was determined by ∆G = -RT ln K b , enthalpy of its interaction (∆Η) and entropy of adduct formation (∆S) were obtained from Van't Hoff equation.

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Section: Reagentsmentioning

confidence: 79%

Thermodynamic Characterization of Dexamethasone Sodium Phosphate and Its Complex With Dna as Studied by Conductometric and Spectroscopic Techniques

Shah

Khan

Usman

et al. 2009

J. Chil. Chem. Soc.

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“…We also demonstrated that the levels of survivin protein expression in HepG2 cells decreased and that the relative activity of caspase-3 significantly increased after treatment with the complex. Hence, our results suggest that the antitumor activity of the [Mn(Que) 2 (H 2 O) 2 ] complex might be related to its intercalation into DNA and its DNA-binding selectivity.…”

Section: Gc (Guanine-mentioning

confidence: 87%

“…Here, the DNA binding properties of the quercetinÀmanganese(II) complex [Mn(Que) 2 (H 2 O) 2 ] were studied using UV/VIS and fluorescence spectroscopy and viscosity measurements. The results indicate that the complex was preferentially bound to DNA in the GC (guanineÀcytosine)-rich regions via an intercalative mode.…”

Section: Gc (Guanine-mentioning

confidence: 99%

GC (Guanine‐Cytosine)‐Selective DNA‐Binding and Antitumor Activity of a QuercetinManganese(II) Complex

Tan

Zhu

Wang

2011

Chemistry & Biodiversity

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The DNA binding and cleavage properties of quercetinÀmanganese(II) complexes have been studied, but little attention has been devoted to the relationship between the antitumor activity of these complexes and the DNA-binding properties. Here, the DNA binding properties of the quercetinÀmanganese(II) complex [Mn(Que) 2 (H 2 O) 2 ] were studied using UV/VIS and fluorescence spectroscopy and viscosity measurements. The results indicate that the complex was preferentially bound to DNA in the GC (guanineÀcytosine)-rich regions via an intercalative mode. Furthermore, the cytotoxicity experiments confirmed its apoptosis-inducing activity. We also demonstrated that the levels of survivin protein expression in HepG2 cells decreased and that the relative activity of caspase-3 significantly increased after treatment with the complex. Hence, our results suggest that the antitumor activity of the [Mn(Que) 2 (H 2 O) 2 ] complex might be related to its intercalation into DNA and its DNA-binding selectivity. It has been reported that the DNA-binding ability of the complex depends upon the planarity of the ligand, the coordination geometry, the ligand donor atom type, and the metal ion type [6]. Some metal complexes, such as ruthenium(II)Àpolypyridyl complexes, preferentially bind to the GC (guanineÀcytosine) sequences in the DNA via intercalation mode and cleave pBR322 DNA [7] [8]. Hence, the development of synthetic, sequence-selective DNA binding and cleavage agents for the processing of DNA and for new potential DNA-targeted antitumor drugs is essential for further expected applications in molecular biology, medicine, and related fields.Quercetin (Que,3,3',4',5,, a bioflavonoid widely distributed in fruits and vegetables, can chelate metal ions to form metal complexes that have better antioxidant and antitumor activities than free quercetin (Que) [5] [8]. In our

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“…Most of acridine compounds are cytotoxic and their toxicity is caused by their DNA binding activity and some of them thus can serve as probes for mutagenesis examination [15,[27][28][29][30][31][32]. In spite of that, cytotoxicity of some acridines may not be connected with their interaction with nuclear DNA but they could induce an ER stress or oxidative stress in cells.…”

Section: Discussionmentioning

confidence: 99%

Intracellular distribution of 3,6-bis(3-alkylguanidino)acridines determines their cytotoxicity

L¹,

Paulíková²,

Bačová³

et al. 2015

neo

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Cytotoxicity of two derivatives of 3,6-bis(3-alkylguanidino)acridines (GNDAs; pentyl-and hexyl-GNDA) was determined against three cell lines: a murine immortalized fibroblast cell line NIH-3T3, a human ovarian carcinoma cell line A2780, and a human neuroblastoma cell line SH-SY5Y. We found out that these GNDAs were cytotoxic against A2780 and NIH-3T3 cells but they showed only a marginal cytotoxicity against neuroblastoma cells SH-SY5Y. To explain differences in cytotoxicity, intracellular distribution of GNDAs was monitored. GNDAs were accumulated in A2780 and NIH-3T3 cells in the nuclei (fluorescence microscopy). In contrast to these cell lines, in SH-SY5Y cells, GNDAs were localized outside of the nuclei, at the plasma membrane and surroundings, extending also to the cytosol. This distribution of GNDAs was confirmed by an ImageStream Flow Cytometer. Acetylcholinesterase (AChE) activity in the SH-SY5Y cells decreased upon incubation with GNDAs. Kinetic studies showed that GNDAs were able to inhibit AChE by the same mode as tacrine (9-amino-1,2,3,4-tetrahydroacridine), a known inhibitor of AChE. A low cytotocity of GNDAs against SH-SY5Y cells could be caused by their affinity to AChE (the enzyme is localized mainly at the plasma membrane). The interaction of GNDAs with AChE may affect their intracellular distribution and consequently the cytotoxicity.

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Cytotoxic activity of proflavine diureas: Synthesis, antitumor, evaluation and DNA binding properties of 1′,1″-(acridin-3,6-diyl)-3′,3″-dialkyldiureas

Cited by 60 publications

References 19 publications

Thermodynamic Characterization of Dexamethasone Sodium Phosphate and Its Complex With Dna as Studied by Conductometric and Spectroscopic Techniques

Thermodynamic Characterization of Dexamethasone Sodium Phosphate and Its Complex With Dna as Studied by Conductometric and Spectroscopic Techniques

GC (Guanine‐Cytosine)‐Selective DNA‐Binding and Antitumor Activity of a QuercetinManganese(II) Complex

Intracellular distribution of 3,6-bis(3-alkylguanidino)acridines determines their cytotoxicity

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