• Title/Summary/Keyword: Quinolone

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Synthesis of 8-Alkoxy-4,5-dihydro-[1,2,4]triazole[4,3-a]quinoline-1-ones and Evaluation of their Anticonvulsant Properties

  • Sun, Xian-Yu;Jin, Yun-Zhe;Li, Fu-Nan;Li, Gao;Chai, Kyu-Yun;Quan, Zhe-Shan
    • Archives of Pharmacal Research
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    • v.29 no.12
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    • pp.1080-1085
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    • 2006
  • A series of 8-alkoxy-4,5-dihydro-[1,2,4]triazole[4,3-a]quinoline-1-one derivatives were synthesized using 7-hydroxy-3,4-dihydro-2(1H)-quinolone as the starting material. Their anticonvulsant activities were evaluated by the maximal electroshock test (MES) and the subcutaneous pentylenetetrazole test (sc-PTZ), and their neurotoxicities were measured by the rotarod neurotoxicity test (Tox). The tests demonstrated that 8-hexyloxy-4,5-dihydro-[1.2.4]triazole[4.3-a]quinoline-1-one (4e) and 8-heptyloxy-4,5-dihydro-[1,2,4]triazole[4, 3-a]quinoline-1-one (4f) were the most potent anticonvulsants, with 4e having $ED_{50}$ values of 17.17 mg/kg and 24.55 mg/kg and protective index ($PI=TD_{50}/ED_{50}$) values of 41.9 and 29.3 in the MES and sc-PTZ tests, respectively, and 4f having $ED_{50}$ values of 19.7 mg/kg and 21.2 mg/kg and PI values of 36.5 and 33.9 in the MES and sc-PTZ tests, respectively. The PI values of 4e and 4f were many fold better than that of the marketed drugs phenytoin, carbamazepine, phenobarbital and valproate, which have PI values in the range of 1.6-8.1 in the MES test and <0.22-5.2 in the sc-PTZ test. Structure-activity relationships were also discussed.

Development of New Quinolone Antibacterials with Dextran-bond (Dextran에 결합된 새로운 Quinolone계 항균제의 개발)

  • Kim, Sun-Il;Na, Jae-Woon
    • Applied Chemistry for Engineering
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    • v.5 no.3
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    • pp.501-508
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    • 1994
  • 1-Ethyl-6-fluoro-1, 4-dihydro-4-oxo-7-(1-piperazinyl)quinolinea-3-car-boxylic acid-dextran was synthesized by the reaction of 1-ethyl-6-fluoro-1, 4-dihydro-4-oxo-7-(1-piperazinyl )quinoline-3-acryloyl chloride with dextran. Polymeric drug was tested for antimicrobial activity in vitro against ten species of microorganisms. Polymeric drug revealed good antibacterial activity against Bacillus subtillis ATCC 6633, Staphyloccus aureus ATCC 25923, Mycrobactertum phlei IFO 3158, Salmonella typhimurium KCTC 1925, Escherichia coli KCTC 1039, Escherichia coli ESS, Klebsiella puemouiae KCTC 1560 and Pseudomonas aeruginosa IFO 13130. Polymeric drug have no antimicrobial against Candida albicans ATCC 10231, but moderately active Micrococcus luteus ATCC 9341.

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Effects of Temperature on the Pharmacokinetics of Norfloxacin inCarp (Cyprinus carpio) and Eel (Anguilla japonica) (수온에 따른 Norfloxacin의 잉어(Cyprinus carpio)와 뱀장어(Anguilla japonica)체내에서 약물동태학적 특성)

  • Kim, Jin-Woo;Jeong, Sung-Hee;Lee, Joo-Seok;Choe, Dong-Lim;Jo, Mi-Ra
    • Journal of fish pathology
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    • v.15 no.2
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    • pp.49-56
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    • 2002
  • Effects of Temperature on the Pharmacokinetics of norfloxecin (NFX) were studied in the cultured carp,Cyprinus carpio, and cel, Anguilla japonica, using high performance liquid chromatography (HPLC) originally developed for quinolone determination in livesrocks. Pharmacokinetics of NFX was apparently affected by ambiem water temperature. In a two-compaament model for carp after oral dosage of 20 mg/K01 at $13^{\circ}C$ and $23^{\circ}C$ and 5.20/hr, respectively. In carp the $K_{\iota\nu}$, $T_{max}$and $C_{max}$ for carp at $13^{\circ}C$ were 13.30/hr, 17.44 ${\mu}g$/$m\ell$ and 7.00 ${\mu}g$/$m\ell$, respectively. The" correspoeding values at $23^{\circ}C$ were 3.93/hr, 15.40 ${\mu}g$/$m\ell$ and 9.44 ${\mu}g$/$m\ell$, respectively. The AUC and T were 355.66 ${\mu}g$ hr/$m\ell$, and 12.70 hr at $13^{\circ}C$ and 417,24 ${\mu}g$ hr/$m\ell$ and 13.86 hrs at $23^{\circ}C$, respectively. Similar trends were revealed in the NFX pharmacokinetics of eel kept under the two water temperature regimes aftee oral NFX dosage of 20 mg/kg. These pharmacokinetkal results have some implication in the optimal usage of recently introduced antibacterials in farmed fish, which were originally adapted for poultry and mammalian species.

Placental Transfer and Pharmacokinetics of a Single Oral Dose of the Fluoroquinolone Antibacterial DW-116 in Rats (랫드에서 fluoroquinolone 항균제 DW-116의 단회 경구투여에 의한 태반통과와 약물동태연구)

  • 김종춘;신호철;허정두;이종화;정문구;윤효인
    • Biomolecules & Therapeutics
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    • v.10 no.1
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    • pp.43-49
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    • 2002
  • The present study was conducted to investigate the placental transfer and pharmacokinetics of the flu-oroquinolone antibacterial DW-116 in pregnant rats. The placental transfer and pharmacokinetics of DW-116 were examined after a single oral dose of 500 mg $^{14}C$ DW-116/kg on gestational day 18. Maternal and fetal tissues were collected at 0.17 0.5,1,2,4,8, and 24 h after dosing. Maximum radioactivity was detected in maternal plasma, placenta, and whole fetus at 1 h, and in amniotic plasma at 4 h after dosing. Thereafter, radioactivity gradually disappeared from these tissues and was 16~28% of maximum levels at 24 h after dosing. Radioactivity in whole fetus were higher than those in the maternal plasma and placenta. The $T_{1/2,abs}$, $T_{1/2,{\beta}},$ AUC, $T_{max},$ and $C_{max}$ in the maternal plasma were approximately 6 min, 13.3 h, 1620 $ug^*hr/ml,$ 0.5 h, and 136 ug/ml, respectively. Those in the placenta were approximately 20 min, 12.3 h, 2150 $ug^*h/$m\ell$,$ 1.0 h, and 172 ug/ml, respectively. Those in the whole fetus were 13 min, 12.8 h,2549 $ug^*h/$m\ell$,$ 1 h, and 191 ug/ml, respectively. In the amniotic fluid of maternal uterus, the 4T_1/2,abs}$, $T1/2,{\beta},$ AUC, $T_{max},$ and $C_{max}$ were approximately 1.3 h,9.3 h,2508 $ug^*h/$m\ell$,$ 4.4 h, and 135 ug/ml, respectively. While DW-116 disappeared biphasically from maternal plasma, whole fetus and placenta, it was eliminated monophasically from amniotic fluid. In conclusion, this study demonstrated that the absorption and distribution of DW-116 in maternal plasma and placenta were extensively rapid, and that the test chemical well passed the blood-placenta barrier and was transferred to the fetus.

Viridicatol from Marine-derived Fungal Strain Penicillium sp. SF-5295 Exerts Anti-inflammatory Effects through Inhibiting NF-κB Signaling Pathway on Lipopolysaccharide-induced RAW264.7 and BV2 Cells

  • Ko, Wonmin;Sohn, Jae Hak;Kim, Youn-Chul;Oh, Hyuncheol
    • Natural Product Sciences
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    • v.21 no.4
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    • pp.240-247
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    • 2015
  • Viridicatol (1) has previously been isolated from the extract of the marine-derived fungus Penicillium sp. SF-5295. In the course of further biological evaluation of this quinolone alkaloid, anti-inflammatory effect of 1 in RAW264.7 and BV2 cells stimulated with lipopolysaccharide (LPS) was observed. In this study, our data indicated that 1 suppressed the expression of well-known pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, and consequently inhibited the production of iNOS-derived nitric oxide (NO) and COX-2-derived prostaglandin E2 ($PGE_2$) in LPS stimulated RAW264.7 and BV2 cells. Compound 1 also reduced mRNA expression of pro-inflammatory cytokines such as $interleukin-1{\beta}$ ($IL-1{\beta}$), interleukin-6 (IL-6), and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$). In the further evaluation of the mechanisms of these anti-inflammatory effects, 1 was shown to inhibit nuclear factor-kappa B ($NF-{\kappa}B$) pathway in LPS-stimulated RAW264.7 and BV2 cells. Compound 1 blocked the phosphorylation and degradation of inhibitor kappa B $(I{\kappa}B)-{\alpha}$ in the cytoplasm, and suppressed the translocation of $NF-{\kappa}B$ p65 and p50 heterodimer in nucleus. In addition, viridicatol (1) attenuated the DNA-binding activity of $NF-{\kappa}B$ in LPS-stimulated RAW264.7 and BV2 cells.

The minimum inhibitory concentration (MIC) of bee venom against bacteria isolated from pigs and chickens (돼지 및 닭에서 분리된 균에 대한 봉독의 최소억제농도(MIC))

  • Kim Soon-Tae;Hwang Ji-Young;Sung Myoung-Suk;Je So-Yang;Bae Dong-Rok;Han Sang-Mi;Lee Sung-Hae
    • Korean Journal of Veterinary Service
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    • v.29 no.1
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    • pp.19-26
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    • 2006
  • Bee venom is synthesized in the venom gland's of worker and queen bees and stored in their venom sacs. Bee venom is a rich source of enzymes, peptides and biogenic amines. there are at least 18 active components in the venom which have some pharmaceutical properties. This study was performed to evaluate minimum inhibitory concentration(MIC) of bee venom against bacteria isolated from pjgs and chickens with disease. In case of reference strains, the MIC $({\mu}g/m{\ell})$ of Staphylococcus aureus ATCC 6538, Streptococcus mutans ATCC 25175, and Salmonella typhimurium ATCC 6538 were 64, 64 and 32, respectively. In case of bacteria isolated from pig and chicken, the MIC of Staphylococcus aureus, Staphylococcus hyicus and Staphylococcus chromogenes were 8, 128 and 128, and that of 11 strains of Escherichia coli were 8 to >512 and that of 8 strains of Salmonella sup were >512. Antibacterial resistance test of 22 strains isolated from pig and chicken and 3 reference strains were performed by agar gel diffusion method, using 17 antibacterial drugs including penicillin, cefazolin, tetracycline and quinolone group. The multiple drug resistant patterns were found in most strains isolated from pig and chicken.

Effects of in vivo Synergism of Eunkyo-san, a Poly-Herbal Formula and Rufloxacin against Klebsiella pneumoniae Respiratory Infections (은교산(銀翹散)과 Rufloxacin의 병용투여(倂用投與)가 Klebsiella pneumoniae 호흡기감염(呼吸器感染)에 미치는 영향)

  • Ho, Yen-Guey;Park, Mee-Yeon;Choi, Hae-Yun;Kim, Jong-Dae;Song, Kwang-Kyu
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.19 no.3
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    • pp.753-759
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    • 2005
  • In order to evaluate the in vivo synergic effect of Eunkyo-san with quinolone antibiotics, rufloxacin (RUFX), the viable bacterial numbers and histopathological changes were monitored after experimental respiratory infection with Klebsiella peumoniae NCTC 9632. The obtained results were as follows : In RUFX group, the viable bacterial numbers were significantly decreased compared to those of control group and these were more dramatically decreased compared to those of single treatment with RUFX, respectively in concomitant treated groups with Eunkyo-san. In control group, severe infiltration of inflammatory cells, hemorrhage and hypertrophy of alveolar linings were demonstrated at microscopical levels. However, these abnormal histopathological changes were significantly decreased compared to those of control group in RUFX group, and these were more dramatically decreased compared to those of single treatment with RUFX, respectively in concomitant treated groups with Eunkyo-san. In RUFX group, the LSA% (luminal surface of alveolar%) were significantly increased compared to those of control group and these were more dramatically decreased compared to those of single treatment with RUFX, respectively in concomitant treated groups with Eunkyo-san. According to these results, it is considered that in vivo antibacterial activity of RUFX group was dramatically increased by concomitant use of Eunkyo-san against K. pneumoniae NCTC 9632 infection of respiratory tract.

Synergic Effect of Mahwangyounpae-tang and Ciprofloxacin on 5 Strains of Aerobic Gram-negative Bacteria (마황윤폐탕(麻黃潤肺湯)과 Ciprofloxacin의 병용(倂用)이 호기성 Gram(-) 세균주(細菌株)에 대한 시험관내(試驗管內) 항균력(抗菌力)에 미치는 영향)

  • Liu, Han-Hsiang;Park, Mee-Yeon;Choi, Hae-Yun;Gu, Deok-Mo;Kim, Jong-Dae;Song, Kwang-Kyu
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.19 no.3
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    • pp.684-689
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    • 2005
  • In order to evaluate the in vitro synergic effect of Mahwangyounpae-tang which was a traditional poly-herbal formula has been used in the treatment of respiratory diseases in oriental medicine, and quinolone antibiotics, ciprofloxacin (CPFX), the minimal inhibitory concentration (MIC), $MIC_{50}$ and MIC90 of single use of quinolones and concomitant treatment with Mahwangyounpae-tang against 5 strains of aerobic gram negative bacteria, Escherichia coli, Klebsiella peumoniae, Hemophilus influenzae, Citrobacter freundii and Pseudomonas aeruginosae. The obtained results were as follows : In the case of aerobic gram negative bacteria, the MIC, $MIC_{50}$ and $MIC_{90}$ against Klebsiella peumoniae and Pseudomonas aeruginosae was significantly decreased in concomitant treated groups with Mahwangyounpae-tang compared to those of single treated groups of CPFX, respectively. However, no significant changes were demonstrated against Echerichia coli, Hemophilus influenzae and Citrobacter freundii. According to these results, it is considered as the in vitro antibacterial activity of CPFX was dramatically increased by concomitant use of Mahwangyounpae-tang against some strains of aerobic gram negative bacteria and the increase and selectivity of antibacterial activities against strains were chosen by the selectivity of Mahwangyounpae-tang not CPFX activity.

Effects of 8-Fluorociprofloxacin And Ciprofloxacin on the Central Nervous System

  • Kim, Young-Hoon;Kim, Dal-Hyun;Choi, Kyung-Eob
    • Toxicological Research
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    • v.8 no.2
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    • pp.161-170
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    • 1992
  • The objectives of this sutdy were to investigate the effects of 8-fluorociprofloxacin(8-FCP) on the central nervous system (CNS) and to compare with those of ciprofloxacin(CP). The $LD_{50}$ values of intravenous 8-FCP were similar or slightly lower in rat (M;203.6mg/kg, F;186.1mg/kg)and markedly lower in mice (M;126.5mg/kg, F;163.1mg/kg), as compared to those of CP. However, no recognizable differences in the clinical signs and recovery were found between 8-FCP and CP in both species. In combination with fenbufen, the convulsive liability of 8-FCP was higher than that of CP. At an intravenous dose of 10mg/kg, 8-FCP provoked convulsive signs and subsequent death in mice, whereas CP produced convulsion at a dose of 40mg/kg. The hexobabital -induced sleeping time was markedly lengthened by the oral administration of 8-FCP, but slightly increased by CP. In addition, the two quinolone derivatives had analgesic effects. The analgesic activity of 8-FCP was approximately two times higher than that at CP. However, both 8-FCP and CP had little effects of pentylenetetrazole-or strychnine-induced convulsion and muscle relaxation. Our finding that 8-FCP had more remarkable CNS effects than CP strongly suggests that there should be differences in the pharmacokinetic characteristics and/or in the binding affinity for specific biologic targets, or receptors, in the CNS.

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In vitro antibacterial activity, postantibiotic effects of norfloxacin and its interaction effects in combination with other antibiotics (시험관내에서 norfloxacin의 항균력과 다른 항생제와 병용투여시 상호작용)

  • Park, Seung-chun;Yun, Hyo-in;Oh, Tae-kwang
    • Korean Journal of Veterinary Research
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    • v.37 no.1
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    • pp.147-154
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    • 1997
  • 국내에서 많이 사용되고 있는 제2세대 quinolone 항생제인 norfloxacin(NFX)에 대한 약역학적인 특성을 구명하기 위하여 국내에서 분리된 동물유래 병원성 세균에 대하여 시험관내에서 실험을 수행하여 다음과 같은 결과를 얻었다. 즉, E coli(n=89) 대한 NFX의 $MIC_{50}$$MIC_{90}$는 공히 0.02g/ml이었으며, Streptococcus spp.(n=36)에 대한 NFX의 $MIC_{50}$는 2g/ml 그리고 $MIC_{90}$는 4g/ml로 나타났다. Salmonella spp.(n=56)에 대한 NFX의 $MIC_{50}$$MIC_{90}$ 모두 0.2g/ml로 강한 항균력을 보였으며, Streptococcus spp.(n=24)에 대한 NFX의 $MIC_{50}$는 2g/ml 그리고 $MIC_{90}$가 4g/ml로 나타났다. Bacillus spp.(n=34)는 NFX의 $MIC_{50}$$MIC_{90}$는 모두 0.4g/ml으로서 대부분의 병원성 세균에 대해서 $MIC_{50}$$MIC_{90}$치가 동일하든지 또는 매우 비슷한 수치를 보여주었다. 그러나 NFX는 혐기성세균인 Clostridium spp.(n=34)에 대해서는 항균력이 매우 낮았다. 현재 수의임상에서 항균제 병용요법이 많이 응용되고 있는 것을 고려하여 NFX와 다른 항생물질간의 분획억제농도 (FICs)를 E coli 88ac을 시험균주로 하여 실험한 결과, NFX와 colistin과 병용할 때 FIC 값이 0.38로서 상승작용을 그리고 gentamicin, trimethoprim, amikacin, penicillin 및 tylosin과의 병용시 FIC 값이 각각 0.52, 0.56, 0.63, 1.00 및 1.02로서 상가작용을 보여주었으며, tetracyclin과의 병용시의 FIC값은 1.49로서 길항작용을 나타냄을 알 수 있었다. 한편 실제 항균제의 임상적용시 매우 주요한 요소인 항균활성후 저농도유효성(PAE)을 알아보기 위하여 E coli AB1157을 시험균주로 측정한 결과 PAE은 0.90~1.02 시간 그리고 S aureus R-209에 대해서는 PAE가 1.58~1.99 시간으로서 그람음성균 및 그람양성균 모두에 대해서 긴 PAE를 갖고 있음을 알 수 있었다.

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