• Proceedings of the Korean Society of Applied Pharmacology
• /
• 1997.04a
• /
• pp.40-47
• /
• 1997

New quinolones generally have a broad antibacterial spectrum against gram-positive, gram-negative, glucose-nonfermenting and anaerobic bacteria. Some of newly developed quinolones have potent activities against S. aureus including MRSA, S.pneumoniae including PRSP, B. fragilis, chlamydiae, mycoplasmas and mycobacteria as well, and show good activities against various strains resistant to antibacterial agents of other classes. Quinolones display postantibiotic effects in vitro and are bactericidal at concentrations similar to or twice that of the minimum inhibitory concentrations (MICs) for susceptible pathogens. In experimental murine infection models including systemic infections with various pathogens such as S. aureus, S. pyogenes, S. pneumoniae, E. coli and P. aeruginosa, quinolones have shown good oral efficacy as well as parenteral efficacy. Good oral absorption and good tissue penetration of quinolones account for good therapeutic effects in clinical settings. The target of quinolones are two structurally related type II topoisomerases, DNA gyrase and DNA topoisomerase IV. Quinolones are shown to stabilize the ternary quinolone-gyrase-DNA complex and inhibit the religation of the cleaved double-stranded DNA. Bacteria can acquire resistance to quinolones by mutations of these target enzymes. Mutation sites and amino acid changes in DNA gyrase and DNA topoisomerase IV are similar in the organisms examined, suggesting that the mechanism of quinolone resistance in the target enzymes is essentially the same among various organisms. Quinolones act on both the target enzymes to different degrees depending on the organisms or agents tested, and bacteria become highly resistant to quinolones in a step-wise fashion. Incomplete cross-resistance among quinolones in some strains of E. coli and S. aureus suggests the possibility of finding quinolones active against quinolone-resistant strains which are prevailing now. To find such quinolones, the potency toward two target enzymes and the membrane permeability including influx and/or efflux systems should be taken into account.

• Bulletin of the Korean Chemical Society
• /
• v.34 no.9
• /
• pp.2675-2679
• /
• 2013

Activity-directed isolation of the methylene chloride fraction from the stems of Parthenocissus tricuspidata have led to the identification of two new compounds (1-2): 1-(2',3',5'-trihydroxyphenyl)-2-(4"-hydroxyphenyl)-ethane-1,2-(E)-epoxide (1, tricuspidatin A) and erythro-1-(3',5'-dihydroxyphenyl)-2-(4"-hydroxyphenyl)-ethane-1,2-diol (2, tricuspidatin B), together with four known compounds (3-6): ${\beta}$-sitosterol (3), nonacosan-1-ol (4), 3-(4-hydroxy-3-methoxyphenyl)-2-propenoic acid hexacosyl ester (5) and betulinic acid (6). Their chemical structures were elucidated based on spectroscopic (IR, UV, MS, 1D and 2D NMR) and physicochemical analyses. Compounds 1 and 2 showed strong DNA topoisomerase II inhibitory activity at both concentrations of 20 and $100{\mu}M$. In addition, 3 exhibited strong cytotoxic activity against the HT-29 and HepG2 cancer cell lines, and 6 showed strong cytotoxicity against the HT-29 and MCF-7 ones.

• Proceedings of the Zoological Society Korea Conference
• /
• 1998.10b
• /
• pp.315.1-315
• /
• 1998

No Abstract, See Full Text

• Proceedings of the Korean Society of Toxicology Conference
• /
• 2001.05a
• /
• pp.9-13
• /
• 2001

Genistein, a natural isoflavonoid phytoestrogen, is a strong inhibitor of protein tyrosine kinase and DNA topoisomerase II activities. Genistein has been shown to have anticancer proliferation, differentiation and chemopreventive effects. In the present study, we have addressed the mechanism of action by which genistein suppressed the proliferation of p53-null human prostate carcinoma cells.(omitted)

• Bulletin of the Korean Chemical Society
• /
• v.27 no.8
• /
• pp.1231-1234
• /
• 2006

• Archives of Pharmacal Research
• /
• v.29 no.7
• /
• pp.541-547
• /
• 2006

Four alkaloids (1-4), three quinolone alkaloids (5-7), and three flavanoid glucosides (8-10) were isolated from the fruits of Evodia officinalis Dode, and their structures were determined from chemical and spectral data. Compounds, 3, 8, 9 and 10 were isolated from this plant for the first time. Of these compounds, 1-3 and 5-7 exhibited moderate cytotoxicities against cultured human colon carcinoma (HT-29), human breast carcinoma (MCF-7), and human hepatoblastoma (HepG-2). Compound 8 showed strong inhibitory effects on DNA topoisomerases I and II (70 and 96% inhibition at a concentration of $20\;{\mu}M$, respectively).

• Proceedings of the PSK Conference
• /
• 2002.10a
• /
• pp.351.2-351.2
• /
• 2002

We have previously reported the synthesis and cytotoxic activities of a series of azaanthraquinone derivatives on the model of doxorubicin(Dox). Dox is known to intercalate into DNA and to inhibit topoisomerase II activity. But in the case of Quinone compounds like Dox. its use is limited because of systemic toxicities. primarily cardiotoxicity and myelosuppression. In this study. we describe the synthesis of benzoquinoxaline derivatives as DACA analogue. DACA has a neutral chromophore and acridine moiety and posions both topoisomerases I and ll with DNA intercalating activity. In order to delineate the SAR of benzoquinoxaline derivatives. an effcient sythetic rout to the target compounds without quinone group. Various attempted removal of quinone from benzoquinoxlinedione was unsuccessful. Diels-Alder rout applied for the synthesis of the target compounds will be discussed.

• Journal of Aquaculture
• /
• v.9 no.1
• /
• pp.93-100
• /
• 1996

Previously, as an effort to make an autonomously replicating expression vector in fish, an ARS (autonomously replicating sequence) was cloned from MAR (matrix attachment region) of Misgurnus mizolepis. The DNA fragment composed of 443 base pairs contains ARS core consensus sequences, topoisomerase II consensus sequences, and A or T box sequences which are homologous to the known consensus sequences originated from other organisms. The clond ARS, as other DNA replication origins, contains inverted repeat sequences and several potential hairpin loop structures. These consensus sequences and hairpin structures may serve as recognition signals for regulatory proteins of DNA replication initiation.

• Journal of Animal Reproduction and Biotechnology
• /
• v.34 no.3
• /
• pp.197-204
• /
• 2019

This study was investigated to test whether the zygote recognized the topoisomerase II beta (TOP2B) mediated DNA fragmentation in epididymal spermatozoa or the nuclease degradation in vas deferens spermatozoa by testing for the presence of gammaH2AX (γH2AX). The γH2AX is phosphorylation of histone protein H2AX on serine 139 occurs at sites flanking DNA double-stranded breaks (DSBs). The presence of γH2AX in the pronuclei of mouse zygotes which were injected with DNA broke epididymal spermatozoa was tested by immunohistochemistry at 5 and 9 h post fertilization, respectively. Paternal pronuclei that arose from epididymal spermatozoa treated with divalent cations did not stain for γH2AX at 5 h. On the other hand, in embryos injected with vas deferences spermatozoa that had been treated with divalent cations, γH2AX was only present in paternal pronuclei, and not the maternal pronuclei at 5 h. Interestingly, both pronuclei stained positively for γH2AX for all treatments and controls at 9 h after sperm injection. In conclusion, the embryos recognize DNA that is damaged by nuclease, but not by TOP2B because H2AX in phosphorylated in paternal pronuclei resulting from spermatozoa treated with fragmented DNA from vas deferens spermatozoa treated with divalent cations, but not from epididymal spermatozoa treated the same way.

• Biomedical Science Letters
• /
• v.12 no.3
• /
• pp.161-170
• /
• 2006

A new piperazine derivative, 8J-8029, is a synthetic anti-cancer agent which exhibits both microtubule and topoisomerase II inhibiting activities. In this study, we investigated the ability of 8J-8029 for anti-angiogenesis and apoptosis. 8J-8029 decreased the bFGF-induced angiogenesis in the CAM and the mouse Matrigel implants, in vivo. 8J-8029 inhibited the proliferation, migration, invasion, tube fonnation, and expression of MMP-2 in BAECs. In addition, 8J-8029 reduced the cell viability in HepG2 cells, caused the production of fragmented DNA and the morphological changes corresponding to apoptosis. 8J-8029 also elicited the release of cytochrome c and the activation of caspase-3. Taken together, these results suggest 8J-8029 may be a candidate for anti-cancer agent with the ability to inhibit the angiogenesis of endothelial cells and to induce the apoptosis of tumor cells.