1,8-Naphthyridine Derivatives. A New Class of Chemotherapeutic Agents

Lesher, George Y.; Froelich, Ernest J.; Gruett, Monte D.; Bailey, John Hays; Brundage, R. Pauline

doi:10.1021/jm01240a021

Cited by 714 publications

(433 citation statements)

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“…The first discovered quinolone was the nalidixic acid (Lesher et al, 1962), which showed activity only against enterobacteria (Nava, 2007). Quinolones emerged accidentally, as a by-product of an antimalarial agent synthesis, with known and proven antibacterial activity, chloroquine.…”

Section: Historicalmentioning

confidence: 99%

Environmental contamination by fluoroquinolones

Frade

Dias

Teixeira

et al. 2014

Braz. J. Pharm. Sci.

142

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Over the past few decades, a high number of pharmaceuticals have been detected in surface, ground and drinking waters. This contamination comes from domestic sewage, livestock, hospitals and chemicalpharmaceutical industries. Typical examples of these pollutants are the fluoroquinolones -powerful antibiotics used in human and veterinary medicine. The presence of fluoroquinolones in the environment can pose a serious threat to the ecosystem and to human health due to their high consumption globally: in 1998, around 120 tons were produced. Even at low environmental concentrations, antibiotics stimulate bacterial resistance. The consequences of the presence of fluoroquinolones in the environment are not fully understood, but are known to be toxic to plants and aquatic organisms. Approximately 85% of the fluoroquinolones present in influents can be removed by conventional wastewater treatment plants, but the removed fraction is frequently accumulated in the sludge, which is sometimes used as fertilizer, representing an additional input route into the environment. The removal of fluoroquinolones by biological treatment is ineffective, and it is believed that only advanced oxidation technologies are able to destroy these emerging pollutants.Uniterms: Fluoroquinolones/waste/environmental impact. Fluoroquinolones/waste/environmental contamination. Environmental contamination. Advanced oxidation processes/wastewater treatment.Nas últimas décadas, um grande número de fármacos tem sido identificado em águas superficiais, subterrâneas e potáveis. Tal contaminação advém do esgoto doméstico, hospitais, criação de animais e das indústrias químico-farmacêuticas. Exemplos típicos desses poluentes são as fluoroquinolonaspotentes antibióticos empregados na medicina humana e veterinária. A presença de fluoroquinolonas no meio ambiente pode representar uma séria ameaça para o ecossistema e para a saúde humana devido ao alto consumo mundial: em 1998 foram produzidas, aproximadamente, 120 toneladas. Mesmo em baixas concentrações, antibióticos podem estimular a resistência bacteriana. As consequências da presença de fluoroquinolonas no ambiente não são completamente compreendidas, mas sabe-se que são tóxicas para plantas e organismos aquáticos. Aproximadamente 85% das fluoroquinolonas presentes em efluentes podem ser removidos em estações de tratamento de efluentes convencionais, porém a fração removida é frequentemente acumulada no lodo, muitas vezes usado como fertilizante, o que representa uma rota adicional de entrada desses compostos no ambiente. A remoção de fluoroquinolonas por meio de tratamento biológico não é eficiente, e acredita-se que somente as tecnologias de oxidação avançada sejam capazes de degradar esses poluentes emergentes.Uniterms: Fluorquinolonas/resíduos/impacto ambiental. Fluorquinolonas/resíduos/contaminação ambiental. Contaminação ambiental. Processos oxidativos avançados/tratamento de águas residuais.

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Section: Historicalmentioning

confidence: 99%

Environmental contamination by fluoroquinolones

Frade

Dias

Teixeira

et al. 2014

Braz. J. Pharm. Sci.

142

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“…The application of the 4-quinolone antibiotic nalidixic acid (l-ethyl-l,4-dihydro-7-methyl-4-oxo-l,8-naphthyridine-3-carboxylic acid) for determination of cell viability was proposed by Kogure et al in 1979 (61). Nalidixic acid, the synthesis of which was reported by Lesher et al (64) in 1962, inhibits DNA replication in most gram-negative bacteria, thereby preventing cell division (35,36). Other cell functions, however, continue to function normally, given that the nalidixic acid concentration is not too high.…”

Section: Flow Cytometrymentioning

confidence: 99%

Assessment of viability of microorganisms employing fluorescence techniques

Breeuwer

Abee

2000

International Journal of Food Microbiology

262

181

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“…During the past decades numerous agents have been synthetised by addition of certain substituents on the basic quinolone ring namely, in position C1 cyclopropyl or difluorophenyl, in position C6 a fluorine and in position C8 a halogen, metoxy or fused third ring. These structure modifications resulted in development of ofloxacin, ciprofloxacin, norfloxacin, levofloxacin, moxifloxacin and several other agents [1][2][3][4]. All above mentioned structure modifications yielded fluoroquinolones and resulted in improved antibacterial efficacy, broaden spectrum and enhanced tissue penetration [5].…”

Section: Commentarymentioning

confidence: 99%

Delafloxacin: A Novel Fluoroquinolone Introduced in Clinical Trials

Kocsis¹,

Szabó²

2016

Int J Clin Med Microbiol

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CommentaryOpen AccessQuinolones were developed and introduced into clinical practice in the 1960s. During the past decades numerous agents have been synthetised by addition of certain substituents on the basic quinolone ring namely, in position C1 cyclopropyl or difluorophenyl, in position C6 a fluorine and in position C8 a halogen, metoxy or fused third ring. These structure modifications resulted in development of ofloxacin, ciprofloxacin, norfloxacin, levofloxacin, moxifloxacin and several other agents [1][2][3][4]. All above mentioned structure modifications yielded fluoroquinolones and resulted in improved antibacterial efficacy, broaden spectrum and enhanced tissue penetration [5].Delafloxacin (WQ-3034) is a novel fluoroquinolone agent, discovered by Wakunaga Pharmaceutical Co., Ltd., Osaka & Hiroshima, Japan. Its chemical structure is 1-(6-amino-3,5-difluoropyridin-2-yl)-8-chloro-6-fluoro-7-(3-hydroxyazetidin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid. This structure has three unique features: lack of a strongly basic group in position C7 that confers weak acidity; a chlorine in position C8 that exhibits a strong electron withdraw on aromatic ring; heteroaromatic substitution in position N1 that leads to a larger molecular surface compared to currently used fluoroquinolones [6]. The anionic structure of delafloxacin increases its potency in acidic environment, therefore its antibacterial activity is enhanced in site of infection with reduced pH (e.g.: skin and soft tissue infections). This feature makes delafloxacin special among fluoroquinolones as ciprofloxacin and moxifloxacin lose potency in acidic environment [7,8]. Delafloxacin is a broad-spectrum agent, as it targets both DNA gyrase and topoisomerase IV enzymes [9]. Based on in vitro testing delafloxacin proved to be effective with MICs between 0.004-0.015 mg/L against various pathogens namely, Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis. Delafloxacin MIC values ranged between 0.12 and 0.5 mg/L against levofloxacin resistant (MIC >4 mg/L) S. pneumoniae strains [10]. Delafloxacin MICs were between 0.008 and 1 mg/L in ciprofloxacin resistant (MIC 0.5-256 mg/L) S. aureus strains [6]. In the case of Neisseria gonorrhoeae delafloxacin exhibited bactericid effect with MICs between 0.001 and 0.25 mg/L that is comparable to those of ceftriaxone (0.001 to 0.25 mg/L) and cefixime (0.001 to 0.5mg/L) [11]. Appart from bactericid effect delafloxacin inhibits biofilm formation of S. aureus [12]. Several murine lung infectious models showed in vivo efficacy of delafoxacin in infections caused by S. aureus, S. pneumoniae and Klebsiella pneumoniae [13,14]. Delafloxacin has been introduced into clinical trials to evaluate its pharmacokinetic properties and to compare its antibacterial efficacy with other antimicrobials. A Phase 1 clinical trial investigated a single per os dose of 900 mg delafloxacin in 30 healthy individuals under different feeding conditions namely, individuals under fasting conditions fo...

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1,8-Naphthyridine Derivatives. A New Class of Chemotherapeutic Agents

Cited by 714 publications

References 1 publication

Environmental contamination by fluoroquinolones

Environmental contamination by fluoroquinolones

Assessment of viability of microorganisms employing fluorescence techniques

Delafloxacin: A Novel Fluoroquinolone Introduced in Clinical Trials

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