• Title/Summary/Keyword: DNA topoisomerase II

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Cytotoxicity and DNA Topoisomerases Inhibitory Activity of Constituents from the Sclerotium of Poria cocos

  • Li, Gao;Xu, Ming-Lu;Lee, Chong-Soon;Woo, Mi-Hee;Chang, Hyun-Wook;Son, Jong-Keun
    • Archives of Pharmacal Research
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    • v.27 no.8
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    • pp.829-833
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    • 2004
  • The bioactivity-guided fractionation of the methylene chloride extract of the sclerotium of Poria cocos led to the isolation of (S)-(+)-turmerone (1), ergosterol peroxide (2), polyporenic acid C (3), dehydropachymic acid (4), pachymic acid (5), and tumulosic acid (6). Compounds 4-6 exhibited moderate cytotoxicities, with $IC_{50}$ values of 20.5, 29.1, and $10.4{\;}\mu\textrm{m}$, respectively, against a human colon carcinoma cell line. However, 3-6 not only showed inhibitory activities as potent as etoposide used as a positive control on DNA topoisomerase II (36.1, 36.2, 43.9 and 66.7% inhibition at a concentration of $20{\;}\mu\textrm{m}$, respectively), but also inhibition of DNA topoisomerase I (55.8, 60.7, 43.5, and 83.3% inhibition at a concentration of $100{\;}\mu\textrm{m}$, respec-tively).

Spectroscopic Studies on Interaction of Protoberberines with the Deoxyoligonucleotide d(GCCGTCGTTTTACA)2

  • Park, Hye-Seo;Kim, Eun-Hee;Kang, Mi-Ran;Chung, In-Kwon;Cheong, Chae-Joon;Lee, Weon-Tae
    • Bulletin of the Korean Chemical Society
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    • v.25 no.10
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    • pp.1559-1563
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    • 2004
  • The topoisomerase II poisoning effect of certain protoberberine alkaloids is associated with anti-cancer activity. Structure-activity relationships of protoberberine analogues substituted on the ring protons reveal that substitution at the C19 position is an important determinant of biological activity. In this study, the effects of substituent modification at the C19 position on the interaction of protoberberines with DNA are determined using UV and NMR spectroscopy. The line broadening effect on aliphatic resonances, chemical shift changes of the imino protons of HP14 upon berberine and berberrubine binding to HP14, and the rate of the exchange process between protoberberine analogs bound indicate that berberrubine binds HP14 more specifically than berberine. In addition, the free HP14 is altered by the substituent at the 19-position. UV spectra of berberrubine have shown a hypochromic effect together with a slight red shift, which are usually regarded as characteristics of DNA intercalation. These results are consistent with our previous report that the berberrubine is partially intercalated with HP14 with molar ratio 1 : 1, whereas a non-specific interaction is predominant between the berberine and HP14.

gyrA and gyrB Mutations in Quinolone-resistant Strains of Enterobacteriaceae Isolated from General Hospitals in Busan

  • Kim, Yun-Tae;Kim, Tae-Un
    • Biomedical Science Letters
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    • v.13 no.2
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    • pp.141-148
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    • 2007
  • We determined the sequences of the quinolone resistance-determining region (QRDR) of gyrA and gyrB for 21 clinical strains of Enterobacteriaceae resistant to ciprofloxacin, norfloxacin and levofloxacin. The clinical strains were isolated from the specimens of three general hospitals in Busan. In the present study, we found mutations in type II topoisomerase (DNA gyrase) genes for all strains. We confirmed that some genera of Enterobacteriaceae of clinical specimen exhibited decreased sensitivity to fluroquinolone due to changes in Ser-83$\rightarrow$Leu and Asp-87$\rightarrow$Asn types on gyrA and alterations in Glu-465$\rightarrow$Arg and Ser-492$\rightarrow$Asn type on gyrB. All the twenty-one strains had a missense mutation in gyrA (codon 83 and 87). Three of them had an additional mutation in gyrB (codon 465 or 492), but one of them had an additional mutation in gyrB (codon 426, 427, 491, 495 and 496). The strains which had two mutations in type II topoisomerase genes (gyrA and gyrB) were significantly more resistant to fluoroquinolones than those with a single mutation in gyrA (mean MICs of ciprofloxacin: $\geq8\mu$g/ml, mean MICs of levofloxacin: $\geq16\mu$g/ml). Interestingly, the examination of silent nucleotide changes n the gyrA and gyrB genes revealed six different patterns of DNA polymorphism, respectively. Fifteen strains of the twenty-one strains bearing the gyrase A mutation shared the same polymorphism and eleven strains of the twenty-one strains bearing the gyrase B mutation shared the same polymorphism.

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Synthesis, Antibacterial, Docking and Anticancer Evaluation of N-Substituted Benzoyl Derivatives

  • Arthi, P.;Shobana, S.;Srinivasan, P.;Rahiman, A. Kalilur
    • Journal of Integrative Natural Science
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    • v.7 no.4
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    • pp.241-252
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    • 2014
  • A series of N-benzoylated ligands incorporating three different benzoyl groups 2,2'-(benzoyliminodiethylene)-4-substituted phenols ($L^{1,4,7}$), 2,2'-(4-nitrobenzoyliminodiethylene)-4-substituted phenols ($L^{2,5,8}$) and 2,2'-(3,5-dinitrobenzoyliminodiethylene)-4-substituted phenols ($L^{3,6,9}$) were synthesized and characterized by IR, $^1H$ NMR, $^{13}C$ NMR and mass spectroscopy. The In vitro antibacterial activity of investigated ligands were tested against human pathogenic bacteria such as four Gram (-) Enterococcus faecalis, Pseudomonas aeruginosa, Staphylococcus aureus, Vibrio cholera, Vibrio harveyi and two Gram (+) Staphylococcus aureus, Streptococcus mutans. Furthermore, docking studies were undertaken to gain insight into the possible binding mode of these compounds with the binding site of the topoisomerase II (PDB: 4FM9) enzyme which is involved in DNA superhelicity and chromosome seggregation. The N-benzoylated derivatives $L^{5,7,8}$ have significant anticancer activity as Topoisomerase inhibitors. The ligands $L^5$ and $L^8$ were tested for their anticancer activity against human liver adenocarcinoma (HepG2) cell line with the MTT assay.

A SURVEY OF N-STRING TANGLE ANALYSES OF DNA-ENZYME SYNAPTIC COMPLEXES

  • KIM, SOOJEONG;MOON, HYEYONG
    • Journal of applied mathematics & informatics
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    • v.35 no.3_4
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    • pp.349-369
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    • 2017
  • In last 30 years, mathematical tangle theory is applied to molecular biology, especially to DNA topology. The recent issues and research results of this topic are reviewed in this paper. We introduce a tangle which models an enzyme-DNA complex. The studies of 2-string tangle equations related to Topoisomerase II action and site-specific recombination is discussed. And 3-string tangle analysis of Mu-DNA complex, n-string tangle analysis ($n{\geq}4$) of DNA-enzyme synaptic complexes are also discussed.

Identification of Radiation-Sensitive Gene in U937 Cell by using cDNA-Chip Composed of Human Cancer Related Gene (U937 세포에서 발암관련 유전자들로 구성된 DNA chip을 이용한 방사선 감수성 유전자들의 선발)

  • 김종수;김인규;강경선;윤병수
    • Environmental Mutagens and Carcinogens
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    • v.22 no.1
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    • pp.54-59
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    • 2002
  • We have used cDNA microarray hybridization to identify gene regulated in response to gamma-irradiation in U-937 cell. The cDNA-chip was composed entirely of 1,000 human cancer related gene including apoptosis and angiogenesis etc. In gamma-irradiated U-937 cell, highly charged protein, ribosomal protein L32, four and a half LIM domains 3, lipocalin 2 (oncogene 24p3) and interleukin 15, ataxia telangiectasia mutated (includes complementation groups A, C and D) genes showed increased level of its transcription, and cell division cycle 25A, dihydrofolate reductase, topoisomerase (DNA) II beta(180kD), kinase suppressor of ras and strarigin genes showed reduced level of its transcription compared to untreated U-937 cell. The significant change of level of transcription was not found in well-known ionizing radiation(IR)-responsive gene, such as transcription factor TP53 and p53 related gene, except ataxia telangiectasia mutated gene.

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Mutation Patterns of gyrA, gyrB, parC and parE Genes Related to Fluoroquinolone Resistance in Ureaplasma Species Isolated from Urogenital Specimens (비뇨생식기계 검체로부터 분리된 Ureaplasma 종의 Fluoroquinolone 내성과 관련된 gyrA, gyrB, parC, parE 유전자의 돌연변이 양상)

  • Cho, Eun-Jung;Hwang, Yu Yean;Koo, Bon-Kyeong;Park, Jesoep;Kim, Young Kwon;Kim, Sunghyun
    • Korean Journal of Clinical Laboratory Science
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    • v.48 no.2
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    • pp.74-81
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    • 2016
  • Ureaplasma species can normally colonize in the bodies of healthy individuals. Their colonization is associated with various diseases including non-gonococcal urethritis, chorioamnionitis, neonatal meningitis, and prematurity. In 2012, the sum of the resistant and intermediate resistant rates of Ureaplasma spp. to ofloxacin and ciprofloxacin was 66.08% and 92.69%, respectively. DNA point mutations in the genes encoding DNA gyrase (topoisomerase II) and topoisomerase IV are commonly responsible for fluoroquinolone resistance. Each enzyme is composed of two subunits encoded by gyrA and gyrB genes for DNA gyrase and parC and parE genes for topoisomerase IV. In the current study, these genes were sequenced in order to determine the role of amino acid substitutions in Ureaplasma spp. clinical isolates. From December 2012 to May 2013, we examined mutation patterns of the quinolone resistance-determining region (QRDR) in Ureaplasma spp. DNA sequences in the QRDR region of Ureaplasma clinical isolates were compared with those of reference strains including U. urealyticum serovar 8 (ATCC 27618) and U. parvum serovar 3 (ATCC 27815). Mutations were detected in all ofloxacin- and ciprofloxacin-resistant isolates, however no mutations were detected in drug-susceptible isolates. Most of the mutations related to fluoroquinolone resistance occurred in the parC gene, causing amino acid substitutions. Newly found amino acid substitutions in this study were Asn481Ser in GyrB; Phe149Leu, Asp150Met, Asp151Ile, and Ser152Val in ParC; and Pro446Ser and Arg448Lys in ParE. Continuous monitoring and accumulation of mutation data in fluoroquinolone-resistant Ureaplasma clinical isolates are essential to determining the tendency and to understanding the mechanisms underlying antimicrobial resistance.