• Bulletin of the Korean Chemical Society
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• 제11권4호
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• pp.323-327
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• 1990

The synthesis and some biological properties of $7{\beta} $-[2-(Z)-(2-aminothiazole-4-yl)-2-(N-substitutedcar bonyl)ethoxyiminoacetamido]-3-vinyl-3-cephem-4- carboxylic acid are described. The effect of substituents on the carbamoly group in the 7-side chain were investigated in order to improve antibacterial activities. Two of these new orally active $7{\beta} $-lactam derivatives showed wide expanded antimicrobial activities against Gram-positive and Gram-negative bacteria, including Pseudomonas aeruginosa, as well as good stability to $7{\beta} $ -lactamases.

• 디지털융복합연구
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• 제13권12호
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• pp.313-318
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• 2015

본 연구에서는 세균의 항균제 내성기전을 연구하기 위해 일개의 대학병원에서 분리된 Enterobacter cloacae를 대상으로 extended spectrum ${\beta}$-lactamase (ESBL) 및 16S rRNA methyltransferase 유전자를 검출하고 항균제 감수성 양상을 조사하였다. 대상균주 중 총 8 균주가 CTX-M-15형 ESBL을 생성하는 것으로 확인되었으며 이 균주들 중 3 균주는 16S rRNA methyltransferase의 한 종류인 armA 유전자도 동시에 가지고 있는 것으로 나타났다. CTX-M-15형 ESBL 유전자와 armA 유전자를 동시에 가지고 있는 E. cloacae는 3세대 cephalosporin 계열 및 aminoglycoside 계열의 항균제 뿐 만 아니라 fluoroquinolone 계열의 항균제에도 내성을 보였다. 더구나 이러한 항균제 내성 유전자들은 플라스미드를 통해 다른 세균으로 전달 될 수 있어 다제내성 세균의 출현 및 확산을 촉진 할 수 있다. 따라서 E. cloacae를 대상으로 지속적인 항균제 내성 유전자를 모니터링 하는 것은 항균제 내성 확산방지를 위해 중요할 것으로 사료된다.

• Journal of Pharmaceutical Investigation
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• 제32권2호
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• pp.73-80
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• 2002

Cefuroxime axetil is a cephalosporin antibiotic having a high activity against a wide spectrum of Grampositive and Gram-negative microorganisms. It is a cephalosporin antibiotic which exist as 2 diastereoisomers: diastereoisomer A and B. It shows polymorphism of three forms: a crystalline form having a melting point of about $180^{\circ}C$, a substantially amorphous form having a high melting point of about $135^{\circ}C$ and a substantially amorphous form having a low melting point of about 70^{\circ}C$. The crystalline form of cefuroxime axetil is slightly soluble in water because diastereoisomer A has lower solubility than B in water. Substantially amorphous form of which there are no difference in solubility between diastereoisomer A and B has better solubility than crystalline form, but it forms a thicker gel than crystalline form upon contact with an aqueous medium. Based on this reason, cefuroxime axetil is not readily absorbable in the gastrointestinal tract, rendering its bioavailability on oral administration very low. The object of this study was to develop an improved non-crystalline cefuroxime axetil composition having a high physicochemical stability and bioavailability. A non-crystalline cefuroxime axetil solid dispersant showing no peak on a Differential Scanning Calorimetry (DSC) scan is prepared by dissolving cefuroxime axetil and a surfactant in an organic solvent; suspending a water-insoluble inorganic carrier in the resulting solution; and spray drying the resulting suspension to remove the organic solvent, said solid dispersant having an enhanced dissolution and stability of cefuroxime axetil and being useful for the preparation of a pharmaceutical composition for oral administration. Tablet was formulated with this cefuroxime axetil solid dispersant, disintegrants and other ingredients. It disintegrated and dissolved easily and dynamically in dissolution medium, so showed a good dissolution profile.

• 한국임상약학회지
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• 제5권2호
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• pp.13-16
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• 1995

The Minimum Inhibitory Concentration (MIC) of a first-generation cephalosporin derivative, Cefazedone (CZD; $PAZERON^R$ inj.) was determined by the two-fold serial agar dilution method. The in-vitro antibacterial activity of CZD against a wide variety of clinical isolates was compared with those of other first generation cephalosporins such as Methylol Cephalexin (CEX), Cefazolin (CEZ), Cefadroxil (CDX), Cephradine (CED), Ceftezol (CTZ) and one of second generation cephalsporin antibiotics, Cefotaxime (CTX). CZD had the most potent inhibitory effect against Gram-positive strains, when compared to the first-generation cephalosporin antibiotics tested in this study and CTX. The geometric MIC mean of CZD for Gram-positive strains was calculated as 0.386 kg/m{\ell}$, and those of CEX, CEZ, CDX, CTZ, CED, and CTX were 6.073, 0.894, 3.399, 0.748, 7.884 and 1.502 $kg/m{\ell}$, respectively. In addition, the geometric mean of CZD for staphylococclJs aureus strains was obtained as 0.340 $kg/m{\ell}$ and those of CEX, CEZ, CDX, CTZ, CED, and CTX 6.145, 0.534, 4.126, 0.442, 10.51, and 2.500 $kg/m{\ell}$, respectively. Against Gram-negative strains, CZD showed better antibacterial activity than CEZ, CDX, CTZ, and CED.

• 대한미생물학회지
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• 제10권1호
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• pp.13-17
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• 1975

저자들은 1967년 이래 '71년, 72년, 73년 4년에 걸쳐 232주의 전형적인 이질균을 동정확인하여 정리한바 있다. 1974년에도 1,504주의 장내 병원성세균이 각 시, 도, 위생시험소 및 종합병원 등에서 수집되어 검사대상이 되었으며 이질균으로 동정확인된 47주를 얻게 되었으므로 그들의 미생물학적 성상을 보고하는 바이다. 서울에서 분리된 shigella flexneri 3주를 제외하고는 강원도에서 44주가 분리되었으며, 그 내역은 sihgella dysenteriae가 1주, shigella flexneri가 43주, shigella sonneri가 3주이었다. 생물학적 성상중 과거에 시험되지 않았던 Christensen's citrate, Sodium acetate, Sodium alginate, Esculin test 등을 시도하였으며 그결과는 미국 Center for Disease Control에서 발표된 성적과 비슷한 결과로 나타났다. 우리나라에서 흔히 상용될 수 있는 항생제에 대한 감수성 검사를 실시하였으며 nitrofurantoin, cephalosporin, ampicillin, penicillin G $1{\mu}g$에 대해서는 1973년도 균주와 마찬가지로 감수성균으로 반응을 보였으며, 반대로 bacitracin, lincomycin, penicillin V $10{\mu}g$에 대해서는 전적으로 내성이 있는 것으로 나타났다. 이 결과들은 예년과 마찬가지로 Ericsson씨 법에 의해 관찰된 것이었다.

• Molecular & Cellular Toxicology
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• 제2권3호
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• pp.193-201
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• 2006

Cephalexin, one of most widely prescribed cephalosporin, has been reported to cause acute renal failure as a side effect in human and experimental animals. Although numerous animal studies have been reported for the cephalosporin nephrotoxicity, the molecular and cellular nephrotoxic mechanisms of cephalexin are still unknown. This investigation evaluated the time-dependent gene expression profile of kidney in mouse during cephalexin induced nephrotoxicity. C57BL/6 female mice were administered either saline or 1,000 mg/kg cephalexin intraperitoneally. Mice were sacrificed at 3, 6, and 24 hr after administration. Blood biochemical and histopathological results indicated cephalexin induced nephrotoxicity. Microarray experiment carried out using Affymetrix $GeneChip^{(R)}$. There were 198 informative genes that were significantly expressed >5-fold versus control at 3, 6, and 24 hr (p<0.01), of which 156 and 42 were up-and down-regulated, respectively. Major classes of up-regulated genes at 3, 6 hr included those involved in MAPK/Jak-STAT signaling pathway and immune response such as cytokine-cytokine receptor interaction and complement and coagulation cascades. At 24 hr, up-regulated genes were mainly involved in regeneration/repair and immune response; down-regulated genes were generally associated with transporters and intermediary metabolism. Among the up-regulated genes at 24 hr, several potential biomarkers on nephrotoxicity such as Kim-1, Fga, Timp1, and Slc34a2 were clustered in a same category. In addition, Tnfrsf12a and Lcn2 which were consistently up-regulated (>5 fold) were also included as potential biomarkers. These results may provide clues for elucidating the mechanism of cephalexin induced nephrotoxicity and evaluating potential biomarkers to assess nephrotoxicity.

• 약학회지
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• 제46권5호
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• pp.313-319
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• 2002

Synthesis of 7$\beta$-[(Z)-2-(2-aminothiazol-4-yl)-2-(1-carboxy-1-methylethoxyimino)acetamido]-3-[[(3S, 5S)-5-[4-phenyl-5-(4-methylphenyl or 2-thiophenyl)-4H-l, 2, 4- triazol-3-yl]thiomethylpyrrolidin-3-yl]]thiomethyl-3-cephem-4-carboxylic acids (7a, 7b) were described. (2S, 4S)-4-acethylthio-2-[4-phenyl-5-(4-methylphenyl or 2-thiophenyl)-4 H-1, 2, 4-triazol-3-yl]thiomethyl-1-tert-butoxycarbonylpyrrolidines (4a, 4b) were prepared from trans-4-hydroxy-L-proline with (2S, 4R)-absolute configuration as starting material. 4-Phenyl-5-(4-methylphenyl or 2-thiophenyl)-4 H-l, 2, 4-triazol-3-thiols (2a, 2b) were prepared from p-toluic anhydride and 2-thiophene carboxylic acid hydrazide, respectively. p-Methoxybenzyl 7$\beta$-(Z)-2-(2-for-mamidothiazol-4-yl)-2-(1-tert-butoxycarbonylisopropylimino]acetamido-3-[[ (3S, 5S)-5-[4-phenyl-5-(4-methylphenyl or 2-thio phenyl)-4H-1, 2, 3-triazol-3-yl]thiomethyl-1- tert-butoxycarbonylpyrrolidin-3-yl]]thiomethyl-3-cephem-4-carboxylates (6a, 6b) were achieved by using p-methoxybenzyl ]7P-(Z)-2-(2-formamidothiazol-4-yl)-2-(tert-butoxycarbonylisopropylimino] acetamido-3-chloromethyl-3-cephem-4-carboxylate (5) and (2S, 4S)-4-acethylthio-2-[4-phenyl-5-(4-methyl phenyl or 2-thiophenyl)-4H-1, 2, 4-triazol-3-yl]thiomethyl-1-tert-butoxycarbonyl pyrrolidines (4a, 4b). Removal of formyl, Boc, and p-methoxybenzyl protecting groups were carried out by triflu oroacetic acid and anisole to give the target compounds.

• 약학회지
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• 제37권2호
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• pp.136-142
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• 1993

To a suspension of 1-cyclopropyl-6,8-difluoro-1,4-dihydro-7-{3,7-diazabicyclo[3.3.0]oct-1(5)-en-3-yl}-4-oxo-3-quinoline carboxylic acid(C1) in sodium hydroxide solution and water is added dropwise with stirring carbon disulfide. [6R-[6$\alpha$, 7$\beta$(Z)]]-7-[[[2-Amino-4-thiazoly)methoxyimino]-acetyl]amino]-3-[[[[7-( 3-carboxy-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxo-7-guinolonyl)-3,7-diazabicyclo[3.3.0]oct-1(5)-en-3-yl]thioxomethyl]thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-2-carboxylic acid (DACD) was synthesized from 1-cyclopropyl-6,8-difluoro-1,4-dihydro-7-[7-(mercapto) thioxomethyl-[3,7-dia zabicyclo[3.3.0]oct-1(5)-en-3-yl}]-4-oxo-3-quinoline carboxylic acid disodium salt(C2) and cefotaxime. The invitro activity of novel dual-action cephalosporin, DACD, was compared with the in vitro activities of CENO(cefotaxime 3'-norfloxacin dithiocarbamate), cefotaxime, and norfloxacin against a variety of bacterial species. In vitro activity of DACD was superior to that of norfloxacin against Streptococcus pyogenes. Against Gram-positive and Gram-negative bacteria, its activity was almost equal to that of CENO.

• 한국미생물·생명공학회지
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• 제13권4호
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• pp.339-344
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• 1985

항세균성 항생제인 세팔로스포린 C가 그 자신의 생산균주인 C. acremonium M-113의 생장을 저해하였다. 비슷한 저해현상이 C. acremonium ATCC 20339와 ATCC 14553에도 관찰되었다. 세팔로스포린C의 최소 생육 저지농도가 분생포자의 경우 200-500$\mu\textrm{g}$/$m\ell$이었고 균사의 경우 3,000-4,000 $\mu\textrm{g}$/$m\ell$이었다. 이 최소 생육 저지농도는 복합배지에서 더욱 상승되었다. 세팔로스포린C는 배양초기에 존재할 경우. 그 생육 저지 효과를 나타내었다. 세팔로스포린 C의 생육 저지 효과는 세팔로스포린 C가 아미노산의 세포 내로의 수송을 방해함으로써 나타나는 것으로 조사되었다. 생육 저지 기저에 세팔로스포린 C의 3' 기가 중요 역할을 하는 것으로 나타났다. 또한, 세팔로스포린 C는 배지에 질소원이 결핍될 때 질소원으로 이용될 수 있는 것으로 나타났다.

• Biomolecules & Therapeutics
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• 제3권4호
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• pp.316-321
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• 1995

All the pharmacological studies of LB17522 described here were carried out with high doses (fifteen to sixty times of the therapeutic dose) to determine an indication of potential side effects in clinical use in terms of the acute clinical signs, cardiovascular and central nervous system. LB10522 does not produce any observable clinical signs except for the symptoms such as moist eye, skin rash, slight salivation, vomitting, and slightly reduced activity. The effects of LB10522 on the hemodynamics and cardiac function of anesthetized beagle dogs are as follows; heart rates and mean arterial blood pressure had a tendency to increase mildly, which is a normal finding in anesthetized dogs. All the animals except for one showed relatively stable respiratory rates throughout the observation period. Each animal treated with LB10522 showed slight increase in the left cardiac work and left ventricular stroke work which are mainly related to corresponding increases in cardiac output. Femoral blood flow were shown to be increased in some animals treated with LB10522. The epileptogenic activities of various cephalosporins were assessed by a direct intracerebral injection of appropriate concentration of test articles. The CD$_{50}$ values (nmol) obtained from the analysis of the dose-response data are as follows; 78.2, 175.3, 156.3, and 53.5 for cefazolin, cephaloridine, ceftazidime, and LB 10522, respectively. LB10522 seems to be equipotent with cefazolin or to be three times more potent than cephaloridine and ceftazidime in causing adverse CNS stimulation. Taken into consideration all the information obtained, LB10522 is not supposed to induce much changes in the functions examined in these studies in man at therapeutic doses.s.