Assessment of DNA-binding affinity of cholinesterase reactivators and electrophoretic determination of their effect on topoisomerase I and II activity

Janočková, Jana; Žilecká, Eva; Kašpárková, Jana; Brabec, Viktor; Soukup, Ondřej; Kuča, Kamil; Kožurková, Mária

doi:10.1039/c6mb00332j

Cited by 7 publications

(4 citation statements)

References 65 publications

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“…For dynamic (collisional) quenching, quencher diffusion to the fluorophore is typical during the lifetime of an excited state and the rate of this quenching is dependent upon temperature, viscosity and diffusion. The decrease of fluorescence in the case of dynamic quenching is due to random collision between the fluorophore and quencher 74 . A Stern–Volmer plot can depend on the mechanism of quenching, and can be non-linear or linear, and upward or downward curving.…”

Section: Resultsmentioning

confidence: 99%

In vitro investigating of anticancer activity of new 7-MEOTA-tacrine heterodimers

Janočková

Korábečný

Plsikova

et al. 2019

Journal of Enzyme Inhibition and Medicinal Chemistry

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A combination of biochemical, biophysical and biological techniques was used to study calf thymus DNA interaction with newly synthesized 7-MEOTA-tacrine thiourea 12 – 17 and urea heterodimers 18 – 22 , and to measure interference with type I and II topoisomerases. Their biological profile was also inspected in vitro on the HL-60 cell line using different flow cytometric techniques (cell cycle distribution, detection of mitochondrial membrane potential dissipation, and analysis of metabolic activity/viability). The compounds exhibited a profound inhibitory effect on topoisomerase activity (e.g. compound 22 inhibited type I topoisomerase at 1 µM concentration). The treatment of HL-60 cells with the studied compounds showed inhibition of cell growth especially with hybrids containing thiourea ( 14–17 ) and urea moieties ( 21 and 22 ). Moreover, treatment of human dermal fibroblasts with the studied compounds did not indicate significant cytotoxicity. The observed results suggest beneficial selectivity of the heterodimers as potential drugs to target cancer cells.

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Section: Resultsmentioning

confidence: 99%

In vitro investigating of anticancer activity of new 7-MEOTA-tacrine heterodimers

Janočková

Korábečný

Plsikova

et al. 2019

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Small organic molecules able to bind DNA provide promises for anticancer activity due to alteration of the structure and function of the genetic material. Amongst a plethora of such binders [1][2][3][4][5][6][7][8], various oxime derivatives were found to show affinity towards DNA [9][10][11][12], whereas others were found to cleave DNA as metal-free artificial nucleases [13,14].…”

Section: Introductionmentioning

confidence: 99%

“…Based on our interest in the chemistry and biology of the oxime functionality [54][55][56][57], as well as in their DNA photolytic interaction upon UV irradiation [9][10][11]43] we have decided to investigate the behaviour of carefully designed O-carbamoyl derivatives of p-pyridine amidoxime, ethanone oxime and aldoxime (VI, VII, VIII, R 1 = p-pyridyl, Figure 1) as DNA photosensitizers. Based on our previous ex-Scheme 1: Synthesis of O-carbamoyl amidoximes (8)(9)(10)(11)(12)(13), ethanone oximes (15)(16)(17)(18)(19)(20) and aldoximes (22)(23)(24)(25)(26)(27). Oxime 1 or 14 or 21, Et 3 N (1.1 equiv), R-NCO (1.1-1.8 equiv), dry chloroform or tetrahydrofuran, Ar, 0 °C → rt or reflux, 19-97%.…”

Section: Introductionmentioning

confidence: 99%

p-Pyridinyl oxime carbamates: synthesis, DNA binding, DNA photocleaving activity and theoretical photodegradation studies

Gritzapis

Varras

Andreou

et al. 2020

Beilstein J. Org. Chem.

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A number of p-pyridinyl oxime carbamate derivatives were prepared upon the reaction of the corresponding oximes with isocyanates. These novel compounds reacted photochemically in the presence of supercoiled plasmid DNA. Structure–activity relationship (SAR) studies revealed that the substituent on the imine group was not affecting the extend of the DNA damage, whereas the substituent of the carbamate group was critical, with the halogenated derivatives to be able to cause extensive single and double stranded DNA cleavages, acting as “synthetic nucleases”, independently of oxygen and pH. Calf thymus–DNA affinity studies showed a good-to-excellent affinity of selected both active and non-active derivatives. Preliminary theoretical studies were performed, in an effort to explain the reasons why some derivatives cause photocleavage and some others not, which were experimentally verified using triplet state activators and quenchers. These theoretical studies seem to allow the prediction of the activity of derivatives able to pass intersystem crossing to their triplet energy state and thus create radicals able to damage DNA. With this study, it is shown that oxime carbamate derivatives have the potential to act as novel effective photobase generating DNA-photocleavers, and are proposed as new leads for “on demand” biotechnological applications in drug discovery and medicine.

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“…DNA binding activity was determined by DNA binding and antitrypanosomal activity as reported previously (21).…”

Section: Dna Binding Activitymentioning

confidence: 99%

Clinical efficacy of recombinant human latrophilin 3 antibody in the treatment of pediatric asthma

Liu¹,

Zhang²,

Liu³

2017

Exp Ther Med

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Abstract. Pediatric asthma is a chronic pulmonary inflammatory disease featuring hypersecretion of mucus and inflammation in the airway, resulting in dysfunction of the airway smooth muscle. Previous evidence demonstrated that latrophilins, a novel family of receptors, present a beneficial effect on airway smooth muscle cells. In the present study, the therapeutic effects of recombinant human latrophilin 3 (rhLPHN3) antibody (Ab) in patients with pediatric asthma were investigated, and the molecular mechanism underlying the function of LPHN3 in the treatment of asthma in clinical practice was examined. A total of 342 pediatric asthma cases were recruited and randomly divided into three groups, receiving treatment with rhLPHN3 Ab (n=134), salbutamol (n=108) or montelukast (n=100) by nasal aerosolization. Each group received the respective clinically tested dose for 16 weeks. Inflammatory factors interleukin (IL)-10, IL-17, IL-4, matrix metallopeptidase-9 (MMP-9), interferon-γ (IFN-γ) and transforming growth factor-β (TGF-β) levels in peripheral blood mononuclear cells were analyzed prior to and post treatment. The clinical outcomes revealed that pathological alterations were significantly improved following treatment with rhLPHN3 Ab for patients with pediatric asthma when compared with those receiving salbutamol and montelukast. It was also observed that rhLPHN3 Ab downregulated the plasma concentration levels of IL-10, IL-17, IL-4 and MMP-9, and upregulated IFN-γ and TGF-β levels in the three groups. In addition, clinical data demonstrated that rhLPHN3 Ab significantly promoted E-selectin and mucin 5AC expression, as well as improved the activation of nuclear factor (NF)-κB p65 DNA binding activity and the phosphorylation levels of protein kinase A. Furthermore, rhLPHN3 Ab markedly improved adhesion and proliferation of airway smooth muscle cells, which led to promotion of the contraction of these cells.In conclusion, these clinical data suggest that rhLPHN3 Ab serves an important role in the inhibition of inflammatory mediators through downregulation of NF-κB signaling pathway, which contributes to airway remodeling and bronchodilation in patients with pediatric asthma.

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Assessment of DNA-binding affinity of cholinesterase reactivators and electrophoretic determination of their effect on topoisomerase I and II activity

Cited by 7 publications

References 65 publications

In vitro investigating of anticancer activity of new 7-MEOTA-tacrine heterodimers

In vitro investigating of anticancer activity of new 7-MEOTA-tacrine heterodimers

p-Pyridinyl oxime carbamates: synthesis, DNA binding, DNA photocleaving activity and theoretical photodegradation studies

Clinical efficacy of recombinant human latrophilin 3 antibody in the treatment of pediatric asthma

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