Disease relevance of Nitracrine

• Behavior of some biochemical components of blood of patients with ovarian carcinoma during Ledakrin treatment [1].
• DNA from the liver nuclei unable to synthesize RNA due to Ledakrin treatment, retained the template activity against E. coli RNA polymerase [2].
• Mutagenic activity of Ledakrin in microbial testing as well as its inductive effect on the release of free phages in lysogenic bacteria were compared with its transforming ability in human cell system [3].
• Results of combined treatment withlung tissue resection and simultaneous administration of Ledakrin in bronchial carcinoma [4].
• In Ehrlich ascites tumour cell nuclei ledakrin (1-nitro-9/3'-dimethylpropyloamine/acridine-2 HCl) induces condensation and margination of chromatin, compaction and segregation of nucleolar components and conglomeration of chromatin granule clusters [5].

High impact information on Nitracrine

• The aim of this work was to characterize the products of metabolic activation of the antitumor drug ledakrin (Nitracrine) in model metabolic systems, where formation of drug-DNA adducts was previously discovered [6].
• Female Wistar rats were injected intraperitoneally with thioacetamide or Ledakrin (1-nitro-9/3'-dimethylpropyloamine/acridine . 2 HCl) to provoke chromatin decondensation or condensation, respectively [7].
• In vitro DNA crosslinking by Ledakrin, an antitumor derivative of 1-nitro-9-aminoacridine [8].
• Using agarose gel electrophoresis we confirmed that Ledakrin is capable of incurring covalent crosslinking in pBR322 plasmid DNA and also in poly(dGdC) in the presence of a simple activating system containing DTT [8].
• Effects of ledakrin on DNA and cell cycle in HeLa S3 cells [9].

Biological context of Nitracrine

• Stimulation of DNA-repair synthesis is gradually shut off during prolonged incubation of the cells with Ledakrin or during postincubation of the cells in a drug-free medium [10].
• The first cross-links were introduced in B. subtilis cell genomes at minimal bactericidal concentrations of Ledakrin of mitomycin C [11].
• DNA damage in HeLa s3 cells by an antitumor drug Ledakrin and other antitumor 1-nitro-9-aminoacridines [10].
• Ledakrin, as compared to mitomycin C, was a very effective cross-linking agent, inducing one covalent cross-link per approx. 20 X 10(3) (B. subtilis), 56 X 10(3) (HeLa) or 80 X 10(3) (Eat) DNA base pairs [11].
• These studies were aimed at characterizing the capability of an antitumor DNA-damaging drug, Ledakrin, and its analogs to inhibit DNA replication in HeLa S3 cells [12].

Anatomical context of Nitracrine

• Ledakrin failed to induce discernible cross-linking of bihelical DNA when complexed with in cell-free system [11].
• Two conclusions have been drawn: 1) the first phase of the response triggered by Ledakrin is due to its action on the cell membrane, 2) the second phase depends on an intracellular mechanism due, probably, to Ledakrin effect on the cytoskeleton [13].
• The obtained results suggest that the external apical cell membrane of epithelial cells is the site of action of Ledakrin [14].
• Blood serum peptidases in patients with ovarian carcinoma treated with Ledakrin [15].
• Ledakrin induces the release of free phages in E. coli K12(lambda +), but does not transform human fibroblasts in cell cuture in vitro [3].

Associations of Nitracrine with other chemical compounds

• Some of Ledakrin -induced DNA breaks are probably generated by endonucleolytic cleavage in the course of repair processes as indicated by experiments with Novobiocin, an antibiotic preventing the incision step of DNA repair [10].
• Unlike [ethyl-14C]quinacrine, compared in vitro, covalent macromolecules binding with Ledakrin in vitro, and most probably in vivo, can be equated to NADPH-dependent activation(s) by oxidoreductase systems and the presence of DNA alone was not satisfactory in itself to attain Ledakrin binding [16].

Gene context of Nitracrine

• An antitumour DNA cross-linking drug, ledakrin, and other antitumour 1-nitro-9-aminoacridines applied to HeLa S3 cells caused a preferential accumulation of cells in S phase, as found by the flow cytometry technique [9].
• The phases G1 and S are prolonged while M is unchanged after 6h incubation with ledakrin [17].
• Analysis of the cell cycle in the root meristem of Allium cepa under the influence of ledakrin [17].
• Ledakrin induced a biphasic action, after a phase of increase of PD, SCC and sodium flux the transport of sodium ions decreased gradually [14].

Analytical, diagnostic and therapeutic context of Nitracrine

• The ledakrin transformation products were separated and analyzed by HPLC with diode array detection [6].
• Localization of DNA in nuclei of the cells labelled with 3H-thymidine and subsequently treated with ledakrin is studied using high-resolution autoradiography [5].

References