Disease relevance of quinacrine

• DHE appears to act as a simple reversible intercalating agent as shown by the selective mutagenic effect on Salmonella TA 1977 tester strain and by its inability to induce the SOS functions in a sfiA lac fusion containing Escherichia coli strain [1].
• A mutation was constructed in the CAP homology domain of yeast topoisomerase II that resulted in hypersensitivity to the intercalating agent N-[4-(9-acridinylamino)-3-methoxy-phenyl]methanesulfonamide and the fluoroquinolone 6, 8-difluoro-7-(4'-hydroxyphenyl)-1-cyclopropyl-4-quinolone-3-carboxyli c acid, but not to etoposide [2].
• Selective inhibition of the cytopathic effect of type A influenza viruses by oligodeoxynucleotides covalently linked to an intercalating agent [3].
• Inhibition of simian virus 40 DNA replication in CV-1 cells by an oligodeoxynucleotide covalently linked to an intercalating agent [4].
• The appearance of nuclear RNA-DNA hybrid molecules and the apparent integration of input virion RNA with host cell DNA was studied using a series of inhibitors of DNA or protein synthesis, cell growth conditions, and an intercalating agent [5].

High impact information on quinacrine

• The transcription signal from the promoter for the 7.5-kilobase rRNA precursor (the gene promoter) is unaffected over a large range of intercalating agent concentrations regardless of whether the template is injected plasmid DNA in oocytes, the amplified endogenous nucleoli of oocytes, or the endogenous chromosomes of cultured Xenopus kidney cells [6].
• Conversely, daunorubicin, an intercalating agent and topoisomerase II inhibitor, induced apoptosis of both resting and activated lymphocytes [7].
• Complexes of the intercalating agent, acridine orange, with double-stranded DNA in situ, emit green fluorescence upon excitation with blue laser light [8].
• By agarose gel electrophoresis, we verified that nafidimide is an intercalating agent, through its alteration of the electrophoretic migration of DNA products produced by the relaxing action of DNA topoisomerase I. Concentrations of up to 100 microM of nafidimide did not produce topoisomerase I-mediated DNA cleavage [9].
• ADR, an intercalating agent and membrane inhibitor, showed a significant depression of PMN degranulation and lysozyme release at 10(-4) and 10(-3) mol/L (15.3% +/- 1.7% v 24% +/- 7%, P less than .01; and 15.0% +/- 2.5% v 24% +/- 7%, P less than or equal to .025) [10].

Chemical compound and disease context of quinacrine

• Echinomycin is a novel bifunctional intercalating agent derived from Streptomyces echinatus [11].
• OBJECTIVES: KW-2170 is a novel DNA intercalating agent whose mechanism of action is similar to doxorubicin HCl, yet is associated with less cardiac toxicity [12].
• Amsacrine is a DNA intercalating agent with antineoplastic properties in lymphoproliferative disorders [13].

Biological context of quinacrine

• We have studied the kinetics of breakage of apurinic (AP) sites by the intercalating agent 9-aminoellipticine using fluorimetric methods with single (ss)- and double (ds)-stranded apurinic DNA [14].
• This was ascribed to stacking interactions of the intercalating agent with base pairs which provide an additional stabilization of the [mRNA/DNA] hybrid [15].
• In particular, EBE-A22 unwinds supercoiled plasmid, stabilizes duplex DNA against heat denaturation, and produces negative CD and ELD signals, as expected for an intercalating agent [16].
• The design of oligonucleotides with an internal intercalating agent might be of interest to control gene expression through recognition of secondary structures in single-stranded targets [17].
• Site-specific cleavage of single-stranded and double-stranded DNA sequences by oligodeoxyribonucleotides covalently linked to an intercalating agent and an EDTA-Fe chelate [18].

Anatomical context of quinacrine

• Cultured human fibroblasts were exposed to various concentrations of actinomycin D, a DNA intercalating agent, and studied by various alkaline elution techniques for the presence of DNA lesions [19].
• Anti-messenger oligodeoxynucleotides covalently linked to an intercalating agent were tested for their ability to inhibit translation of Trypanosoma brucei mRNAs in a cell-free system [20].
• P2.1 mutant cells were generated from a Jak1-minus, HT1080 fibrosarcoma-derived cell line (U4C) after extensive mutagenesis with the intercalating agent ICR191 [21].

Associations of quinacrine with other chemical compounds

• Here we show that gamma-H2AX foci were also formed when cells were incubated with 0.5 microg/ml DNA intercalating agent actinomycin D [22].
• In isolated nucleoli from Tetrahymena thermophila, low concentrations of the intercalating agent proflavine inhibit both transcription termination and splicing of the rRNA precursor [23].
• The degree of supercoiling was varied using the intercalating agent chloroquine and evaluated from fluorescence microscopy images [24].
• Echinomycin: the first bifunctional intercalating agent in clinical trials [25].
• Nitracrine (NC) is an electron affinic DNA intercalating agent and a potent hypoxia-selective cytotoxin and radiosensitizer in cell culture [26].

Gene context of quinacrine

• The prognostic value of BCRP and Pgp were analyzed in the whole population and according to intercalating agent [27].
• alpha-DNA X: alpha and beta tetrathymidilates covalently linked to oxazolopyridocarbazolium (OPC): comparative stabilization of oligo beta-[dT]:oligo beta-[dA] and oligo alpha-[dT]:oligo beta-[dA] duplexes by the intercalating agent [28].

Analytical, diagnostic and therapeutic context of quinacrine

• Piroxantrone, a synthetic intercalating agent, was studied in patients with advanced, measurable gastric adenocarcinoma who had not received prior chemotherapy [29].
• The interaction between oligo-alpha-thymidylates covalently linked to an intercalating agent (an acridine derivative) and their complementary sequences containing beta-nucleosides (poly(rA), poly(dA), r(Ap)7rA, p(dA)8) has been studied using circular dichroism spectroscopy [30].
• We have used DNA colony hybridization, the polymerase chain reaction (PCR), and direct DNA sequencing to determine the mutations induced by the intercalating agent ellipticine in Salmonella typhimurium TA98 in the presence of S9 [31].

References