New spiro tria(thia)zolidine⿿acridines as topoisomerase inhibitors, DNA binders and cytostatic compounds

Salem, Othman; Vilková, Mária; Janočková, Jana; Jendželovský, Rastislav; Fedoročko, Peter; Žilecká, Eva; Kašpárková, Jana; Brabec, Viktor; Imrich, Ján; Kožurková, Mária

doi:10.1016/j.ijbiomac.2016.02.018

Cited by 30 publications

(12 citation statements)

References 49 publications

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“…15 Salem et al described thiazolidinone-acridines as new potential anticancer agents. 84 These compounds exhibited DNA-binding abilities and topoisomerase I and II inhibition. The most active derivative was 2-(acridin-9-yl)imino-3diphenylamino-1,3-thiazolidin-4-one (130) (Scheme 20), which inhibited topoisomerase II at the concentration of 5 mM.…”

Section: Inhibitors Of Human Carbonic Anhydrase Isozymes Based On Acrmentioning

confidence: 99%

“…68 Bharathi et al presented the synthesis, solvatochromic behaviour and larvicidal activity of substituted ethyl 10-chloro-4-(3,4dimethoxyphenyl)-2-hydroxy-12-phenyl-1,4,5,6-tetrahydro-benzo[a]acridine-3-carboxylates (85a-e). 69 Derivatives (85a-e) were obtained by reaction of (E)-7-chloro-2-(3,4-dimethoxybenzylidene)-9-phenyl-3,4-dihydroacridin-1(2H)-ones (83a-e) with ethyl acetoacetate (84) in the presence of 10% ethanolic NaOH (Scheme 11). 69 Derivatives (85b and 85e) showed good larvicidal activities against A. stephensi (LC 50 126.3 and 108.17 mg L À1 , respectively) and H. maculata (LC 50 111.57 and 241.05 mg L À1 , respectively).…”

Section: Inhibitors Of Human Carbonic Anhydrase Isozymes Based On Acrmentioning

confidence: 99%

“…The regioisomeric product (131) demonstrated lower activity against HL-60 cancer cells compared to (130). 84 Gao et al reported the synthesis of benzimidazole acridine derivatives (136a-p). 85 9-Chloroacridine derivatives (134a-l) were obtained by cyclization of the anthranilic acids (133a-l), which were synthesized by the Ullmann condensation.…”

Section: Inhibitors Of Human Carbonic Anhydrase Isozymes Based On Acrmentioning

confidence: 99%

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Recent developments in the synthesis and biological activity of acridine/acridone analogues

2017

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Section: Inhibitors Of Human Carbonic Anhydrase Isozymes Based On Acrmentioning

confidence: 99%

Section: Inhibitors Of Human Carbonic Anhydrase Isozymes Based On Acrmentioning

confidence: 99%

Section: Inhibitors Of Human Carbonic Anhydrase Isozymes Based On Acrmentioning

confidence: 99%

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Recent developments in the synthesis and biological activity of acridine/acridone analogues

2017

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“…The interaction between external molecules and DNA leads to significant changes in its structure and therefore to perturbations in its CD spectra [34,40]. The effect of IAA on the conformation of the secondary structure of ctDNA was investigated by CD study.…”

Section: Resultsmentioning

confidence: 99%

New Insights into Structural and Functional Roles of Indole-3-acetic acid (IAA): Changes in DNA Topology and Gene Expression in Bacteria

et al. 2019

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Indole-3-acetic acid (IAA) is a major plant hormone that affects many cellular processes in plants, bacteria, yeast, and human cells through still unknown mechanisms. In this study, we demonstrated that the IAA-treatment of two unrelated bacteria, the Ensifer meliloti 1021 and Escherichia coli, harboring two different host range plasmids, influences the supercoiled state of the two plasmid DNAs in vivo. Results obtained from in vitro assays show that IAA interacts with DNA, leading to DNA conformational changes commonly induced by intercalating agents. We provide evidence that IAA inhibits the activity of the type IA topoisomerase, which regulates the DNA topological state in bacteria, through the relaxation of the negative supercoiled DNA. In addition, we demonstrate that the treatment of E. meliloti cells with IAA induces the expression of some genes, including the ones related to nitrogen fixation. In contrast, these genes were significantly repressed by the treatment with novobiocin, which reduces the DNA supercoiling in bacterial cells. Taking into account the overall results reported, we hypothesize that the IAA action and the DNA structure/function might be correlated and involved in the regulation of gene expression. This work points out that checking whether IAA influences the DNA topology under physiological conditions could be a useful strategy to clarify the mechanism of action of this hormone, not only in plants but also in other unrelated organisms.

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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%

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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New spiro tria(thia)zolidine⿿acridines as topoisomerase inhibitors, DNA binders and cytostatic compounds

Cited by 30 publications

References 49 publications

Recent developments in the synthesis and biological activity of acridine/acridone analogues

Recent developments in the synthesis and biological activity of acridine/acridone analogues

New Insights into Structural and Functional Roles of Indole-3-acetic acid (IAA): Changes in DNA Topology and Gene Expression in Bacteria

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

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