3,6-Bis(3-alkylguanidino)acridines as DNA-intercalating antitumor agents

Plsikova, Jana; Janovec, Ladislav; Kovaľ, Ján; Ungvarsky, Jan; Mikes, Jaromír; Jendželovský, Rastislav; Fedoročko, Peter; Imrich, Ján; Kristián, Pavol; Kašpárková, Jana; Brabec, Viktor; Kožurková, Mária

doi:10.1016/j.ejmech.2012.09.020

Cited by 44 publications

(34 citation statements)

References 71 publications

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“…Thus, the determination of K b and the number of binding sites (n) of the supramolecular complex formed between the β-carbolines evaluated and ctDNA was performed from a fluorimetric titration. 35 These parameters were calculated according to the following equation (equation 2 Figures 1b and 1c show the profiles of the curves for compound 3b from the linearization of the equations 1 and 2, respectively.…”

Section: Evaluation Of Ctdna Interaction Applying Spectroscopy Methodsmentioning

confidence: 99%

Interaction of β-Carbolines with DNA: Spectroscopic Studies, Correlation with Biological Activity and Molecular Docking

Silva

Savariz

Silva-Júnior

et al. 2016

Journal of the Brazilian Chemical Society

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Quantitative interaction of twelve β-carboline derivatives with calf thymus deoxyribonucleic acid (ctDNA) using spectroscopic techniques was evaluated. The values of the binding constants (K b ) obtained for the complexes formed with the ctDNA ranged from 3.30 × 10 2 to 1.82 × 10 6 mol L −1 , being the β-carbolines with the N,N-dimethylaminophenyl group at position 1 the ones which presented the highest K b values. The binding mode between the β-carbolines evaluated and ctDNA was proposed from the KI assay, competition with ethidium bromide, and DNA thermal denaturation profile (T m ), where it was possible to infer that the evaluated alkaloids interact with ctDNA preferably via intercalation. Additionally, the correlation of K b values obtained with the IC 50 of seven human cancer cell lines was carried out. From this study, it was possible to observe a linear relation among most of the evaluated derivatives, obtaining r 2 values from 0.5360 to 0.9600. In addition, in silico molecular docking was performed to corroborate the experimental results.

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Section: Evaluation Of Ctdna Interaction Applying Spectroscopy Methodsmentioning

confidence: 99%

Interaction of β-Carbolines with DNA: Spectroscopic Studies, Correlation with Biological Activity and Molecular Docking

Silva

Savariz

Silva-Júnior

et al. 2016

Journal of the Brazilian Chemical Society

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“…The observed linear increase in viscosity as a function of chalcone content for all compounds across the range of the relation of chalcone--DNA concentrations, suggests the fact that the interaction of the compounds with the DNA leads to increase the length of the DNA chains, which is indicative of the classical intercalation model. 18,19 Figure 3. Electronic titration spectra of chalcones with CD-DNA , a) C1, b) C2 , c) C3 , d) C4 , e) …”

Section: Resultsmentioning

confidence: 99%

“…On the other hand, a groove binder, typically carries out subtle changes and the DNA remains in the unperturbed form and not increase of the DNA length is observed, therefore this binding mode shows no increase of the viscosity of the DNA solutions. 18,19 In the herein work, the effect of the increasing concentration of chalcones over the relative viscosity of CT-DNA at room temperature …”

Section: Viscositymentioning

confidence: 99%

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Interaction of Chalcones With Ct-Dna by Spectrophotometric Analysis and Theoreticalsimulations

et al. 2016

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publicado na web em 08/07/2016 Chalcones are open chain molecules precursors of flavonoids and isoflavonoids, found spread in edible plants. Because they are easily accessible trough Claisen Shmidt condensation, a great variety of derivatives are available. They have also shown potential in pharmacological and biological applications. It is known that chalcone derivatives display a role in the treatment of complex diseases such as cancer, among others, where the DNA is considered as the target for the action of these kinds of compounds. This action is commonly explained as the inhibition of the DNA replications and transcriptions through interactions. However, not conclusive associations between these DNA-Drug interactions and toxicity have been found. This research focuses on the capacity of a chalcone`s family to interact with DNA. Therefore, the binding constants for each compounds with Calf Thymus DNA [CT-DNA] were determined by spectrophotometric titration at room temperature. In addition, the effect of increasing the chalcone`s concentration over the relative viscosity of CT-DNA at room temperature was assessed. On the other hand, with the aim to find the optimal DNAchalcone configurations, as well as consistently predict their binding, a computational work was undertaken. To accomplish these goals within a reasonable time framework, an empirical scoring function (AScore) and a docking engine (ShapeDock) were performed using the ArgusLab package. The results of viscosity and docking measurement provided structural insights which suggest that chalcones bind with DNA via interaction as well as intercalation. The presence of interactions is also evidenced by the spectrophotometric study which showed luminescence quenching of the chalcones upon interaction with CT-DNA.

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“…1, GNDAs) were synthesized in the Department of Organic Chemistry, Faculty of Science, University in Kosice as hydrochloride salts [16].…”

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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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3,6-Bis(3-alkylguanidino)acridines as DNA-intercalating antitumor agents

Cited by 44 publications

References 71 publications

Interaction of β-Carbolines with DNA: Spectroscopic Studies, Correlation with Biological Activity and Molecular Docking

Interaction of β-Carbolines with DNA: Spectroscopic Studies, Correlation with Biological Activity and Molecular Docking

Interaction of Chalcones With Ct-Dna by Spectrophotometric Analysis and Theoreticalsimulations

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

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