• Journal of Microbiology
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• 제39권1호
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• pp.62-66
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• 2001

Unlike eukaryotic efflux pumps energized by ATPase bacterial efflux pumps are energized by the proton motive force. That is the reason why CCCP, an inhibitor of proton motive forcer is widely used to study the bacterial efflux pump. In many cases, efflux systems have been observed only in quinolone-resistant bacteria. Most of the quinolone-susceptible strains have been found to maintain little efflux pump. However some susceptible bacteria skewed the increased intracellular quinolone concentration only at a low concentration (0.01 or 0.1 mM) but net at a high concentration (1 mM) of CCCP. If bacterial cells were killed at high concentrations of CCCP and lost the integrity of their membranes, the intracellular quinolone would leak out from cells with no efflux system. The efflux pump system in the quinolone-susceptible strains could net be detected at the same concentration used for resistant bacteria. To test this hypothesist the intracellular quinolone concentration in the quinolone-susceptible and -resistant strains of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus was assayed at various concentrations of CCCP. Since the effect of CCCP is very rapid, the survival of bacteria was observed by assaying the DNA synthesis in 5 min. In the case of E. coli, but not P. aeruginosa or S. aureus, the quinolone susceptible strain was more susceptible to CCCP than the quinolone resistant ones, especially when the incubation with CCCP was extended. Decrease of the intracellular quinolone concentration resulted in a false result-no or weak efflux system in the quinolone susceptible strains. Results suggested that the concentration of CCCP should be optimized in order to detect the efflux system in the quinolone susceptible strains of E. coli.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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• pp.221-221
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• 1994

The cross-coupling reaction of organo tin reagents with a variety of organic halides, catalyzed by palladium, provides a novel method for generating a carbon-carbon bond. We use this method for antibacterial agents, and synthesis of new quinolone derivatives which have carbon-carbon bond at C-7 position of general quinolone moieties. Aryl tin, quinolone moieties, and palladium catalyst were refluxed in DMF to afford new quinolone derivatives. This palladium catalyzed coupling reactions have capacity for further synthetic elaboration.

• 약학회지
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• 제37권6호
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• pp.615-620
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• 1993

The cross-coupling reaction of organo tin reagents with a variety of organic halides, catalyzed by palladium, provides a novel method for generating a carbon-carbon bond. We used this method for the antibacterial agents, and synthesis of new quinolone derivatives which have carbon-carbon bond at C-7 position of general quinolone moieties. Aryl tin, quinolone moieties, and palladium catalyst were refluxed in DMF to afford new quinolone derivatives. This palladium catalyzed coupling reactions have capacity for further synthetic elaboration.

• 생약학회지
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• 제49권2호
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• pp.108-112
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• 2018

Four quinolone alkaloids, 2-heptyl-4-quinolone (1), 2-nonyl-4-quinolone (2), 2-undecyl-4-quinolone (3), and 2-undecen-1'-yl-4-quinolone (4), together with two nitrogen derived benzoic acid derivatives, N-acetylanthranilic acid (5) and o-acetamidobenzamide (6) have been isolated from the Arctic bacterial strain, Pseudomonas aeruginosa. The structures of the compounds were determined by 1D and 2D NMR, and MS experiments, as well as by comparison of their data with published values. To the best of our knowledge, compounds 3-6 were isolated for the first time from P. aeruginosa.

• Bulletin of the Korean Chemical Society
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• 제17권1호
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• pp.90-93
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• 1996

• 미생물학회지
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• 제50권3호
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• pp.185-190
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• 2014

원유시료에서 분리한 대장균의 quinolone 항생제 내성비율과 그 내성 결정인자를 분석하였다. 원유시료에서 대장균을 분리하고 quinolone 항생제인 nalidixic acid와 ciprofloxacin에 대한 MIC값을 결정하였으며 내성균을 대상으로 염색체상에 있는 quinolone 내성 결정부위(quinolone resistant determining region, QRDR)인 gyrA, gyrB, parC, pareE의 염기서열 분석, 플라스미드상에 존재하는 내성유전자(plasmid mediated quinolone resistant, PMQR) qnrA, qnrB, qnrS, aac(6')-lb-cr, qepA의 분석 및 약물 유출펌프 유전자인 acrB의 발현을 비교 분석하였다. 그 결과 총 487개의 대장균군 세균중 9개의 균이 nalidixic acid에 내성임을 확인하였으며($MIC{\geq}64{\mu}g/ml$) 이중 6개 균주가 ciprofloxacin에도 내성임을 확인하였다(MIC $4-16{\mu}g/ml$)). 9개의 내성 균주 모두 QRDR의 gyrA 영역 codon 83에 변이(S83L)를 갖고 있었으며 그 중 2균주는 codon 83과 87 (S83L and D87N)에 이중 돌연변이를 갖고 있었다. 한편 9균주 중 3개의 균주에서 parC 영역 codon 80 (S80I)에 변이를 갖고 있었다. 플라스미드 상에 존재하는 내성유전자인 qnrA, qnrB, qnrS, aac(6')-lb-cr 및 qepA 유전자는 존재하지 않았으며 AcrAB-TolC efflux pump 유전자인 acrB 유전자가 대조균인 E. coli ATCC 25922와 비교하여 ciprofloxacin 내성 균주 6균주 중 4균주에서 유의적으로 과발현(2.15-5.74배) 되고 있음을 확인하였다.

• Archives of Pharmacal Research
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• 제29권5호
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• pp.369-374
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• 2006

An efficient method for the synthesis of optically active 2-substituted 2,3-dihydro-4-quinolones has been developed. The key features include the introduction of a chiral side chain and the construction of quinolone skeleton by Mitsunobu alkylation and hydroarylation, respectively.

• 약학회지
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• 제47권5호
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• pp.283-287
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• 2003

Isoflavonoids are abundant in natural products and reported with many synthetic variations. However, relatively few quinolone analogs of isoflavonoids have been described. As part of our endeavor to pursue biologically active novel isoflavonoids, we report an efficient synthetic route for quinolone analogs of isoflavonoids. The key intermediate, 2'-aminochalcone 2 was obtained from substituted aniline and cyclized to afford quinolones 6, 8a, and 8b.

• 대한임상검사과학회지
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• 제50권4호
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• pp.422-430
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• 2018

퀴놀론 항균제가 사람과 동물에게 부적절하고 광범위하게 사용될 경우 항균제내성인자의 출현 및 확산이 가속화 될 수 있다. 본 연구에서는 돼지의 직장면봉 검체(N=40) 및 임상 검체로(N=25)부터 분리된 총 65균주의 nalidixic acid 내성 대장균을 대상으로 quinolone 내성 기전을 조사하였다. 항균제 감수성은 디스크 확산법에 의해 결정되었다. Quinolone 내성과 관련된 유전자와 돌연변이를 조사하기 위해 PCR 및 DNA sequencing이 수행되었다. 총 65균주의 nalidixic acid 내성 대장균 중 62균주가 gyrA, parC, parE 유전자에 돌연변이를 포함하고 있었는데, gyrA 유전자에 돌연변이를 포함하고 있는 균주는 62균주(95.4%)였고, 35균주(53.8%)가 parC 유전자에 돌연변이를 갖고 있었으며, 7균주(10.8%)가 parE 유전자에 돌연변이를 포함하고 있었다. 35균주는 gyrA 와 parC 유전자에 모두 돌연변이를 가지고 있는 것으로 나타났다. 총 65균주의 대장균을 대상으로 plasmid-mediated quinolone resistance (PMQR) determinants를 조사하였다. 65균주의 nalidixic acid 내성 대장균 중 13균주에서 qnrS 유전자가 검출되었으나 이 중 10균주는 gyrA, parC, parE 유전자에 돌연변이를 포함하고 있는 것을 나타났다. 본 연구에서는 사람과 돼지로부터 분리된 대장균이 quinolone 계열 항균제에 내성을 나타내는데 중요한 역할을 하는 기전이 gyrA, parC, parE 유전자에 염색체 돌연변이가 발생하는 경우임을 확인하였는데 이 돌연변이들은 치료목적 또는 동물의 성장촉진을 위한 항균제의 과다사용으로 유발될 수 있다.

• Biomolecules & Therapeutics
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• 제7권2호
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• pp.164-169
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• 1999

The synthesis and antimicrobial activity of N-substituted glycol derivatives of Norfloxacin were described. Norfloxacin was treated with chloroacetyl chloride to yield chloroacetyl norfloxacin (1). This compounds was reacted with alkyldiamines to afford bivalent ligand quinolone carboxylic acids (2-6), which was added to pivaloyloxymethyl chloride to give bivalent ligand pivaloyloxymethyl quinolone carboxylates (7-11). Chloroacetyl norfloxacin (1) treated with alkylamines to obtain monovalent ligand quinolone carboxylic acids (12-15), which was reacted with pivaloyloxymethyl chloride to get monovalent ligand pivaloyloxymethyl quinolone carboxylates (16-19). Free carboxylic quinolones (2-6, 12-15) showed little stronger activities to their pivaloyloxymethyl esters (7-11, 16-19). In monovalent ligand quinolone analogues, longer a1kyl chain com-pounds showed stronger activities than shorter one.