Cytotoxic 3,6-bis((imidazolidinone)imino)acridines: Synthesis, DNA binding and molecular modeling

Janovec, Ladislav; Kožurková, Mária; Sabolová, Danica; Ungvarsky, Jan; Paulíková, Helena; Plsikova, Jana; Vantová, Zuzana; Imrich, Ján

doi:10.1016/j.bmc.2011.01.012

Cited by 83 publications

(35 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results are also in the reverse order of those of the acridine mono-and bisacridine derivatives, in which it had been discovered that the binding constants decreased with increasing substituent length [38][39][40][41]. It is possible to suggest that the different values in comparison to those of the acridine-DNA complexes are caused by the distinct geometry of the tacrine-DNA complexes, and by a different type of binding with DNA.…”

Section: Absorption Measurementmentioning

confidence: 57%

Tacrine derivatives as dual topoisomerase I and II catalytic inhibitors

Janočková

Plsikova

Kovaľ

et al. 2015

Bioorganic Chemistry

Self Cite

View full text Add to dashboard Cite

Section: Absorption Measurementmentioning

confidence: 57%

Tacrine derivatives as dual topoisomerase I and II catalytic inhibitors

Janočková

Plsikova

Kovaľ

et al. 2015

Bioorganic Chemistry

Self Cite

View full text Add to dashboard Cite

“…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. Such types of acridines were prepared in our laboratory [33][34][35]. It was proven that 3,6-bis((1-n-alkyl-5-oxo-imidazolidin-2-yliden) imino)acridine hydrochlorides were localized in mitochondria [36].…”

Section: Discussionmentioning

confidence: 99%

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

L¹,

Paulíková²,

Bačová³

et al. 2015

neo

View full text Add to dashboard Cite

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.

show abstract

“…12,30 It is known that DNA intercalators can significantly interfere with these shows the absorbance changes upon increasing complex concentration.…”

Section: Topoisomerase I Inhibitionmentioning

confidence: 99%

Synthesis, in vitro DNA interactions, cytotoxicities, antioxidative activities, and topoisomerase inhibition potentials of Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) complexes with azo-oxime ligands

Ayvaz¹,

Turan²,

Dural³

et al. 2017

Turk J Chem

View full text Add to dashboard Cite

Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) transition metal complexes of 2-hydroxy-5-[(E)-(4-phenyl) diazenyl]benzaldehyde oxime and 2-hydroxy-5-[(E)-(4-nitrophenyl) diazenyl] benzaldehyde oxime ligands were synthesized and characterized through NMR, IR, ESI mass, and UV analysis. DNA binding abilities of the complexes were revealed using a UV-Vis spectrophotometer with the absorption titration and competitive binding techniques. Hydrolytic and oxidative DNA cleavage activities under different conditions were also proved. Topoisomerase I inhibition efficiencies and in vitro free radical scavenging activities of all complexes were examined. Finally, the selective cytotoxic potentials of all complexes were evaluated in human colon cancer, normal colon, and fibroblast cell lines using the water-soluble tetrazolium salt (WST-1) assay. The complexes had the ability to intercalate into stacked base pairs of DNA and topoisomerase I activity was reasonably inhibited in their presence in 0.4 mM concentrations. The abilities for scavenging of DPPH and hydroxyl radicals were found to be higher than those of known standard antioxidants (ascorbic acid, butylated hydroxyanisole, and mannitol). The results obtained from the cytotoxicity experiments are especially promising for further research, which must be carried out for the evaluation of the studied complexes as anticancer drugs.

show abstract

Cytotoxic 3,6-bis((imidazolidinone)imino)acridines: Synthesis, DNA binding and molecular modeling

Cited by 83 publications

References 32 publications

Tacrine derivatives as dual topoisomerase I and II catalytic inhibitors

Tacrine derivatives as dual topoisomerase I and II catalytic inhibitors

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

Synthesis, in vitro DNA interactions, cytotoxicities, antioxidative activities, and topoisomerase inhibition potentials of Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) complexes with azo-oxime ligands

Contact Info

Product

Resources

About