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Papers by Jana Janockova

Research paper thumbnail of Inhibition of DNA topoisomerases I and II and growth inhibition of HL-60 cells by novel acridine-based compounds

European Journal of Pharmaceutical Sciences, 2015

HL-60 cancer cells were treated with a series of novel acridine derivatives (derivatives 1-4) in ... more HL-60 cancer cells were treated with a series of novel acridine derivatives (derivatives 1-4) in order to test the compounds' ability to inhibit both cancer cell growth and topoisomerase I and II activity. Binding studies of derivatives 1-4 with calf thymus DNA were also performed using a number of techniques (UV-Vis and fluorescence spectroscopy, thermal denaturation, linear dichroism and viscometry) to determine the nature of the interaction between the compounds and ctDNA. The binding constants for the complexes of the studied acridine derivatives with DNA were calculated from UV-Vis spectroscopic titrations (K = 3.1 Â 10 4 -2.0 Â 10 3 M À1 ). Some of the compounds showed a strong inhibitory effect against Topo II at the relatively low concentration of 5 lM. Topo I/II inhibition mode assays were also performed and verified that the novel compounds are topoisomerase suppressors rather than poisons. The biological activities of derivatives were studied using MTT assay and flow cytometric methods (detection of mitochondrial membrane potential, measurement of cell viability) after 24 and 48 h incubation. The ability of derivatives to impair cell proliferation was tested by an analysis of cell cycle distribution.

Research paper thumbnail of Tacrine derivatives as dual topoisomerase I and II catalytic inhibitors

Bioorganic Chemistry, 2015

This study examines the binding properties of a series of newly synthetized tacrine derivatives 1... more This study examines the binding properties of a series of newly synthetized tacrine derivatives 1-4 and their anticancer effects. Spectroscopic techniques (UV-Vis, fluorescence spectroscopy, thermal denaturation, and linear spectropolarimetry) and viscometry were used to study DNA binding properties and to determine the types of DNA interaction with the studied derivatives. The binding constants for the complexes with DNA were obtained using UV-Vis spectroscopic titrations (K = 1.6 Â 10 4 -4.0 Â 10 5 M À1 ) and electrophoretic methods were used to determine the effect of the derivatives on topoisomerase I and II activity. Monotacrine derivative 1 showed evidence of topoisomerase I relaxation activity at a concentration of 30 Â 10 À6 M, while bistacrine derivatives 2-4 produced a complete inhibition of topoisomerase I at a concentration of 5 Â 10 À6 M. The biological activities of the derivatives were studied using MTT-assay and flow cytometric methods (detection of mitochondrial membrane potential and measurement of cell viability) following incubation of 24 and 48 h with human leukemic cancer cell line HL60. The ability of the derivatives to impair cell proliferation was also tested through the analysis of cell cycle distribution.

Research paper thumbnail of Novel cholinesterase modulators and their ability to interact with DNA

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2013

Research paper thumbnail of Interaction of cholinesterase modulators with DNA and their cytotoxic activity

International Journal of Biological Macromolecules, 2014

This research was focused on a study of the binding properties of a series of cholinesterase reac... more This research was focused on a study of the binding properties of a series of cholinesterase reactivators compounds K075 (1), K027 (2) and inhibitors compounds K524, K009 and 7-MEOTA (3-5) with calf thymus DNA. The nature of the interactions between compounds 1-5 and DNA were studied using spectroscopic techniques (UV-vis, fluorescence spectroscopy and circular dichroism). The binding constants for complexes of cholinesterase modulators with DNA were determined from UV-vis spectroscopic titrations (K = 0.5 × 10 4 -8.9 × 10 5 M −1 ). The ability of the prepared analogues to relax topoisomerase I was studied with electrophoretic techniques and it was proved that ligands 4 and 5 inhibited this enzyme at a concentration of 30 M. The biological activity of the novel compounds was assessed through an examination of changes in cell cycle distribution, mitochondrial membrane potential and cellular viability. Inhibitors 3-5 exhibited a cytotoxic effect on HL-60 (human acute promyelocytic leukaemia) cell culture, demonstrated a tendency to affect mitochondrial physiology and viability, and also forced cells to accumulate in the G 1 /G 0 -phase of the cell cycle. The cholinesterase reactivators 1 and 2 were found relatively save from the point of view of DNA binding, whereas cholinesterase inhibitors 3-5 resulted as strong DNA binding agents that limit their plausible use.

Research paper thumbnail of Inhibition of DNA topoisomerases I and II and growth inhibition of HL-60 cells by novel acridine-based compounds

European Journal of Pharmaceutical Sciences, 2015

HL-60 cancer cells were treated with a series of novel acridine derivatives (derivatives 1-4) in ... more HL-60 cancer cells were treated with a series of novel acridine derivatives (derivatives 1-4) in order to test the compounds' ability to inhibit both cancer cell growth and topoisomerase I and II activity. Binding studies of derivatives 1-4 with calf thymus DNA were also performed using a number of techniques (UV-Vis and fluorescence spectroscopy, thermal denaturation, linear dichroism and viscometry) to determine the nature of the interaction between the compounds and ctDNA. The binding constants for the complexes of the studied acridine derivatives with DNA were calculated from UV-Vis spectroscopic titrations (K = 3.1 Â 10 4 -2.0 Â 10 3 M À1 ). Some of the compounds showed a strong inhibitory effect against Topo II at the relatively low concentration of 5 lM. Topo I/II inhibition mode assays were also performed and verified that the novel compounds are topoisomerase suppressors rather than poisons. The biological activities of derivatives were studied using MTT assay and flow cytometric methods (detection of mitochondrial membrane potential, measurement of cell viability) after 24 and 48 h incubation. The ability of derivatives to impair cell proliferation was tested by an analysis of cell cycle distribution.

Research paper thumbnail of Tacrine derivatives as dual topoisomerase I and II catalytic inhibitors

Bioorganic Chemistry, 2015

This study examines the binding properties of a series of newly synthetized tacrine derivatives 1... more This study examines the binding properties of a series of newly synthetized tacrine derivatives 1-4 and their anticancer effects. Spectroscopic techniques (UV-Vis, fluorescence spectroscopy, thermal denaturation, and linear spectropolarimetry) and viscometry were used to study DNA binding properties and to determine the types of DNA interaction with the studied derivatives. The binding constants for the complexes with DNA were obtained using UV-Vis spectroscopic titrations (K = 1.6 Â 10 4 -4.0 Â 10 5 M À1 ) and electrophoretic methods were used to determine the effect of the derivatives on topoisomerase I and II activity. Monotacrine derivative 1 showed evidence of topoisomerase I relaxation activity at a concentration of 30 Â 10 À6 M, while bistacrine derivatives 2-4 produced a complete inhibition of topoisomerase I at a concentration of 5 Â 10 À6 M. The biological activities of the derivatives were studied using MTT-assay and flow cytometric methods (detection of mitochondrial membrane potential and measurement of cell viability) following incubation of 24 and 48 h with human leukemic cancer cell line HL60. The ability of the derivatives to impair cell proliferation was also tested through the analysis of cell cycle distribution.

Research paper thumbnail of Novel cholinesterase modulators and their ability to interact with DNA

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2013

Research paper thumbnail of Interaction of cholinesterase modulators with DNA and their cytotoxic activity

International Journal of Biological Macromolecules, 2014

This research was focused on a study of the binding properties of a series of cholinesterase reac... more This research was focused on a study of the binding properties of a series of cholinesterase reactivators compounds K075 (1), K027 (2) and inhibitors compounds K524, K009 and 7-MEOTA (3-5) with calf thymus DNA. The nature of the interactions between compounds 1-5 and DNA were studied using spectroscopic techniques (UV-vis, fluorescence spectroscopy and circular dichroism). The binding constants for complexes of cholinesterase modulators with DNA were determined from UV-vis spectroscopic titrations (K = 0.5 × 10 4 -8.9 × 10 5 M −1 ). The ability of the prepared analogues to relax topoisomerase I was studied with electrophoretic techniques and it was proved that ligands 4 and 5 inhibited this enzyme at a concentration of 30 M. The biological activity of the novel compounds was assessed through an examination of changes in cell cycle distribution, mitochondrial membrane potential and cellular viability. Inhibitors 3-5 exhibited a cytotoxic effect on HL-60 (human acute promyelocytic leukaemia) cell culture, demonstrated a tendency to affect mitochondrial physiology and viability, and also forced cells to accumulate in the G 1 /G 0 -phase of the cell cycle. The cholinesterase reactivators 1 and 2 were found relatively save from the point of view of DNA binding, whereas cholinesterase inhibitors 3-5 resulted as strong DNA binding agents that limit their plausible use.

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