• Title/Summary/Keyword: Acriflavine

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Genotoxicity Studies of the Complex of Acriflavine and Guanosine (Acriflavine과 Guanosine 복합체(AG60)의 유전독성시험)

  • 정영신;홍은경;김상건;안의태;이경영;강종구
    • Environmental Mutagens and Carcinogens
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    • v.22 no.2
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    • pp.106-111
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    • 2002
  • AG6O, the complex of acriflavine and guanosine, has been shown to possess the synergistic antitumorigenic activity in the previous paper (J. Pharm. Pharmacol. 1997, 49:216). In this study, we have investigated the genotoxic properties of AG60 using in vitro and in vivo system such as Ames bacterial reversion test, chromosomal aberration assay and micronucleus assay. In Ames reverse mutation test, AG60 treatment at the dose range up to 250 $\mu\textrm{g}$/plate caused the dose-independent random induction of the mutagenic colony formation in S. typhimurium TA98, TA100, TA1537, and E. coli WP2uvrA, while any mutagenic effect of AG60 wasn't observed in S. typhimurium TA1535. Any significant chromosomal aberration wasn't observed in chinese hamster lung (CHL) fibroblast cells incubated with PBS or AG60 at the concentrations of 2.5, 5, 10 $\mu\textrm{g}$/$m\ell$ for 24 hours without but even with 59 metabolic activation system for 6 hours. In vivo ICR mice, the intramuscular injection of AG60 at the doses of 7.15, 14.3, and 28.6 mg/kg did not induce the frequency of micronucleus formation. However, mitomycin C, as one of the positive controls at the dose of 2 mg/kg caused the 8.4% induction in the frequency of micronucleus and 24% increase in the chromosomal aberration.

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Curing Action of Antibiotic Resistant Factor in Bacillus Subtilis (Bacillus subtilis의 항생물질 내성에 대한 Curing작용)

  • Hong, Yong-Ki;Seu, Jung-Hwn
    • Microbiology and Biotechnology Letters
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    • v.13 no.2
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    • pp.103-107
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    • 1985
  • A variety of plasmid curing agents such as sodium dodecyl sulfate, acriflavine, ethidium bromide, and mitomycin-C were used to cure Bacillus subtilis cells of streptomycin resistant factor. The drug susceptibility was increased by 0.1% sodim dodecyl sulfate at stationary growth phase. The curing frequency was obtained highly at 4 $\mu\textrm{g}$/$m\ell$ of acriflavine, 10 $\mu\textrm{g}$/$m\ell$ of ethidium bromide, and 200 $\mu\textrm{g}$/$m\ell$ of mitomycin-C. respectively. Curing action occurred competitively for the streptomycin and terramycin resistant factors in B. subtilis.

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Strain Improvement of Streptomyces minoenisis DMCJ-144, An ${\alpha}$-Amylase Inhibitor Producing Actinomycetes (알파-아밀라제 저해제 생산 방선균 Streptomyces minoensis DMCJ-144의 균주개량)

  • 최응칠;김숙경;강동희;이재우;김병각
    • Biomolecules & Therapeutics
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    • v.1 no.1
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    • pp.26-30
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    • 1993
  • Strain of treptomyces minoensis DMCJ-144 was tried to be improved so that it produces much more the $\alpha$-amylase inhibitor. Streptomyces minoensis DMCJ-144 was treated with 1 mg/mι (pH 9.0) of N-methyl-N'-nitro-N-nitrosoguanidine at $30^{\circ}C$ for 60 min and irradiated with UV light distanced 30 cm for 20 min. After mutagenesis, surviving colonies were cultured on the CM contaning acriflavine ($10{\mu}g/ml$) three times in order to enhance the mutability. And then through multi-level screening, colonies that ${\alpha}$-amylase inhibitor productibility. was Improved were selected by modified-blue value method. After third acriflavine treatment, $\alpha$-amylase inhibitory activities of selected colonies were found to be much better as compared with that of parent strain. One mutant strain showed 5.4 time inhibitory activity than the parent strain.

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STUDIES ON THE AGGLUTINATION REACTION OF BRUCELLA R-FORM BY ACRIFLAVIN AND HEAVY METAL IONS (Acriflavine 및 중금속이온반응에 의한 Brucella R형균 검출에 관한 연구)

  • Kang Byong-Kyu
    • Journal of the korean veterinary medical association
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    • v.10 no.1
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    • pp.13-23
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    • 1966
  • 1. To evaluate the quantitative relationship between S-R variation in 8r. abortus strain 19 and Br. melitensis 16 M induced by homologous immune serum treatment was studied by means of tube agglutination reaction with acriflavine add various heavy metal i

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Elucidation of photo-induced electron transfer in a loop-forming peptide: Dye-Ala-Gly-Gln-Tyr

  • Lee, Hwiin;Kim, Jeongyun;Kwon, Yong-Uk;Lee, Minyung
    • Rapid Communication in Photoscience
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    • v.4 no.3
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    • pp.59-62
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    • 2015
  • We investigated photo-induced electron transfer (PET) in a dye-labeled peptide, fluorophore-Ala-Gly-Gln-Tyr, employing time-resolved fluorescence. As an effort to develop new functional dyes, we studied an acriflavine derivative for the electron-acceptor in the excited state from tyrosine, an electrondonor in the ground-state. The pH dependence of the fluorescence lifetime of the model peptide indicates that electron transfer between the excited dye and tyrosine occurs when the tyrosine is deprotonated. The proton-coupled electron transfer appears to be sequential rather than concerted. We also report direct time measurements on the end-to-end loop formation processes of the peptide in water.

Distribution of Acriflavine in Rats Following Intramuscular Administration of a Mixture of Acriflavine and Guanosine, a Potential Antitumor Agent (신규 항암성 화합물 아크리플라빈과 구아노신 복합체를 흰쥐에 근육주사시 아크리플라빈의 체내분포)

  • Song, Suk-Gil;Chung, Youn-Bok
    • YAKHAK HOEJI
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    • v.50 no.1
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    • pp.8-14
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    • 2006
  • A 1 : 1 mixture of acriflavine (ACF; CAS 8063-24-9) and guanosine is currently being evaluated as a possible antitumor agent in preclinical studies. Guanosine is known to potentiate the anticancer activity of some compounds. However, the distributions of trypaflavine (TRF) or proflavine (PRF) have not been investigated in mammals. We, therefore, investigated the distribution of TRF and PRF after i.m. administration of the combination mixture (ACF and guanosine) at a dose of 30 mg/kg ACF in rats. to analyze TRF and PRF levels in biological samples, we used an HPLC-based method. The calibration curves for TRF and PRF in the samples were linear over the concenration range of $0.05{\sim}200\;{\mu}g/ml$. The intra- and inter-day assay accuracies of this method were within ${\pm}15\%$ of norminal values and the precision did not exceed $15\%$ of relative standard diviation. The lower limits of quantitation were 50 ng/ml for both TRF and PRF. The distribution of TRF or PRF was determined by 48 h after i.m. administration of the combination mixture at a dose of 30 mg/kg ACF. TRF and PRF were distributed as the following order; kidney>lung>liver>small intestine>muscle. Of the various tissues, TRF and PRF were mainly distributed to the kidney and lung. The concentrations of TRF or PRF in the tissues 24 h after i.m. administration decreased to undetectable levels. The concentrations of TRF or PRF in the blood cells were comparable to those for the plasma. However, the concentrations of TRF or PRF in the both plasma and blood cells 12 h after i.m. administration were not detected. The number of the platelets in the 1 ml of the blood was calculated to be $0.183{\times}10^8/ml$ of blood. The PRF concentration in platelets was higher than that of TRF at initial times after i.m. administration of the combination mixture. However, both the TRF and PRF concentrations in the plateles 24 h after i.m. administration of the combination mixture were below the quantifiable limit. In conclusion, the concentrations of TRF or PRF in the various tissues, plasma, blood cells, and plateles decreased to undetectable levels 24 h after i.m. administration of the combination mixture at a dose of 30 mg/kg ACF.

General Pharmacology of AG 60, a New Anticancer Drug (새로운 항암제 AG 60의 일반약리작용)

  • 성연희;안희열;김선돈;이선애;조순옥;한영복
    • Biomolecules & Therapeutics
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    • v.5 no.4
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    • pp.412-418
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    • 1997
  • General pharmacological properties of AG 60 (mixture of acriflavine and guanosine (1:1, w/w)), which has anticancer effect, following intramuscular administration were examined in terms of effects on central nervous system, gastrointestinal system, cardiovascular system, respiratory system and autonomic nervous system in mice, rats, guinea-pigs and rabbits. AG 60 at the dose of 15 mgtg had no influences on pentobarbital sleeping time, spontaneous motor activity, chemoshock produced by pentylenetetrazole solution, writhing syndromes induced by 0.8% acetic acid solution, and motor coordination of mice. However, AG 60 at the dose of 7.5 and 15 mg/kg caused significant decrease of normal body temperature 1 and/or 2 h after the administration. No influence on body temperature was observed at 3.75 mg/kg in mice. Gastric secretion of rat and intestinal motility of mice were not influenced by the dose of 15 mg/kg. In terms of autonomic nervous system, AG 60 did not show direct effect and inhibitory or augmentative action of histamine- or acetylcholine-induced contractions at the concentration of 5 mg/L in the isolated ileum of guinea-pig. The administration of 15 mg/kg of AG 60 did not affect mean arterial blood pressure and heart rate in rat. AG 60 (15 mg/kg) given to anesthetized rabbits showed no effect on respiratory rate.

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The R-Plasmid Transfer and Elimination of Shigella Cultures (Shigella균속의 항균제내성, 전달성 R-plasmid 및 제거에 관한 연구)

  • Hong, Sung-Ro;Lee, Yun-Tai
    • The Journal of the Korean Society for Microbiology
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    • v.21 no.1
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    • pp.33-45
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    • 1986
  • On hundred and forty stains of shigella cultures isolated from the twelve hygiene laboratories of cities and provincial general hospital laboratories in 1983 were tested for their resistance to thirteen antimicrobial drugs and their R-plasmid transfer. Antimicrobial drugs were used amikacin, ampicillin, cephalothin, chloramphenicol, gentamicin, kanamycin, nalidixic acid, rifampicin, streptamycin, tetracycline, tobramycin, cefoperazone and piperacillin. All strains were resistant to one or more of thirteen antimicrobial drugs but 94.3% were susceptible to amikacin, gentamicin and tobramycin of total isolated. The most strains commonly found resistance was to chloramphenicol (94%) followed by streptamycin (93%), tetracyline (92%) piperacillin (90%) ampicillin (83%), cefoperazone (42%), nalidixic acid (14%), cephalothin (17%), rifampicin (22%) and kanamycin (6%), sixty percent of strains among 140 were resistance to ampicillin, chloramphenicol, streptomycin, tetracycline at the same time. The transfer of drug resistance by conjugation was tested and ninety four strains (94.3%) were resistant to one or more drugs were found to transfer their drug resistance of E. coli. percentage of transfer frequency by conjugation was one strains (54%), the transfer frequency of drug resistance varied by donor strains and recipients, but not by selecting drugs. Resistance to nalidixic acid was not transferred by conjugation to recipients. Percentage of plasmid curing after the treatment of acriflavine, acridine orange was about 8%. Among strains cured two strains were tested compare original strains with them in biochemical properties in arginine dihydrolase and arabinose fermentation reaction. It was found to growth curves of No.2 shigella flexneri, serotype 1b, and its derivatives cured with acriflavine in $M{\ddot{u}}ller$ Hinton broth medium (pH 7.4, $38^{\circ}C$) by temperature Gradient Biophoto Recorder TN-1120 (Tokyo, Japan).

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Elimination of R-Plasmid in Streptomyces bobili (YS-40) by Ethldium Bromide (Ethidium Bromide에 의한 Streptomyces bobili(YS-40)의 R-Plasmid 제거)

  • 김상달;도재호
    • Microbiology and Biotechnology Letters
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    • v.10 no.4
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    • pp.289-295
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    • 1982
  • Streptomyces bobili (YS-40) isolated from soil was tested that it had drug resistance against penicillin, cephalosporin series antibiotics and other antibiotics in the previous paper. The treatment of Streptomyces bobili, (YS-40) with ethidium bromide (EtBr), acriflavine and sodium dodecyl sulfate. (SDS) resulted in the elimination of R-plasmid from the host strain. Minimum growth inhibitory concentrations (MIC) of Hg, Ag, penicillin-G, ampicillin, chloramphenicol, oxytetracycline, streptomycin and kanamycin were found to be 15, 10, > 3, 000, > 100, > 1, 000, > 100, < 5 and < 5$\mu\textrm{g}$/$m\ell$ respectively. Among the curing agents, EtBr was proved to be the most powerful compound for the elimination of R-plasmid in the strain and the elimination rate with EtBr(10$\mu\textrm{g}$/$m\ell$) was about 98%. Optimal pH to. the elimination of R-plasmid was pH 7.0 and the R-plasmid in the cells incubated for 24 hrs was proved to be eliminated most effectively. Aerial mass color, soluble pigment formation and reverse side color were reported to be often the plasmid associated characteristics of the R-plasmid bearing bacteria. But these characteristics of the uncured and cured Streptomyces bobili, (YS-40) showed no changes in the most of the pigment formation media tested in this work.

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Ultrastructural Alterations in the Gastric Mucous Epithelial Cells of Mouse Inoculated with Ehrlich Carcinoma Cells, Induced by 5-Fluorouracil, Mitomycin C or Acriflavine-Guanosine Compound (AG60) (5-Fluorouracil, Mitomycin C 및 Acriflavine-Guanosine 복합제가 Ehrlich 암세포를 이식한 생쥐 위점막 점액상피세포의 미세구조에 미치는 영향)

  • Ko, Eun-Ju;Park, Kyung-Ho;Park, Dae-Kyoon;Kim, Duk-Soo;Ko, Jeong-Sik
    • Applied Microscopy
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    • v.41 no.1
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    • pp.1-11
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    • 2011
  • This experiment was performed to evaluate the morphological responses of the gastric epithelial cells of the mouse, inoculated with Ehrlich carcinoma cells in the inguinal area, following administration of 5-fluorouracil, mitomycin C or Acriflavine-Guanosine compound (AG60). In this study, each mouse was inoculated with $1{\times}10^7$ Ehrlich carcinoma cells subcutaneously in the inguinal area. From next day after inoculations, 0.2 mL of saline, 5-fluorouracil (30 mg/kg), mitomycin C ($400{\mu}g/kg$) or AG60 (30 mg/kg) were injected to the animals every other day, respectively. Each animals were sacrificed after 7th injection and tissue were taken from the gastric mucosa. Thereafter, the ultrathin sections were stained with uranyl acetate and lead citrate. In the 5-fluorouracil-, mitomycin C- or AG60-treated mice, myelin figures and multivesicular bodies within the gastric mucous epithelial cells were observed more frequently than those of the normal control. In the 5-fluorouracil-treated mice, membrane structures containing a few mucous granules in the luminal space were observed. Indeed, bulging cytoplasmic process containing mucous granules protruding into the gastric lumen were observed in the mitomycin Ctreated mice. Therefore, this study suggested that AG60 as compared with 5-fluorourail and mitomycin C may effective medicine without damage to the secretion ability of gastric mucous epithelial cells.