Antibacterial Agents

Anderson, Rosaleen J.; Groundwater, Paul W.; Todd, Adam; Worsley, Alan J.

doi:10.1002/9781118325421

Cited by 73 publications

(63 citation statements)

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“…The nitroimidazole or nitrofuranyl anion formed upon reduction may either undergo decomposition to produce NO or become further reduced to nitroso and hydroxylamine intermediates [4]. In the present studies, the levels of free NO were either absent or too low to be detected, which leads us to speculate that in C. difficile the nitroheterocyclic anions of metronidazole and nitrofurantoin do not undergo decomposition.…”

Section: Discussionmentioning

confidence: 54%

“…However, based on studies in other organisms, metronidazole is bioreductively activated by cellular oxidoreductases (e.g. nitroreductases), whereby its nitro group is reduced by an electron to produce a highly reactive and unstable nitroimidazole anion that can have several fates [4]. The unstable nitroimidazole anion may be further reduced to nitroso and hydroxylamine intermediates or may undergo decomposition yielding additional reactive species in the form of an imidazole radical and a nitrite anion from which nitric oxide (NO) is derived [4].…”

Section: Introductionmentioning

confidence: 99%

“…nitroreductases), whereby its nitro group is reduced by an electron to produce a highly reactive and unstable nitroimidazole anion that can have several fates [4]. The unstable nitroimidazole anion may be further reduced to nitroso and hydroxylamine intermediates or may undergo decomposition yielding additional reactive species in the form of an imidazole radical and a nitrite anion from which nitric oxide (NO) is derived [4]. These nitroimidazole reactive derivatives and NO cause damage to cellular targets, namely proteins and DNA, leading to cell death [4,5].…”

Section: Introductionmentioning

confidence: 99%

“…The unstable nitroimidazole anion may be further reduced to nitroso and hydroxylamine intermediates or may undergo decomposition yielding additional reactive species in the form of an imidazole radical and a nitrite anion from which nitric oxide (NO) is derived [4]. These nitroimidazole reactive derivatives and NO cause damage to cellular targets, namely proteins and DNA, leading to cell death [4,5]. If NO is produced upon metronidazole bioreduction in C. difficile , this might indicate that it imposes nitrosative stress in C. difficile in a manner similar to the innate immune system [6].…”

Section: Introductionmentioning

confidence: 99%

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Action of nitroheterocyclic drugs against Clostridium difficile

Kumar

Adhikari

Hurdle

2014

International Journal of Antimicrobial Agents

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The nitroheterocyclic classes of drugs have a long history of use in treating anaerobic infections, as exemplified by metronidazole as a first-line treatment for mild-to-moderate Clostridium difficile infection (CDI). Since direct comparisons of the three major classes of nitroheterocyclic drugs (i.e. nitroimidazole, nitazoxanide and nitrofurans) and nitrosating agents against C. difficile are under-examined, in this study their actions against C. difficile were compared. Results show that whilst transient resistance occurs to metronidazole and nitazoxanide, stable resistance arises to nitrofurans upon serial passage. All compounds killed C. difficile at high concentrations in addition to the host defence nitrosating agent S-nitrosoglutathione (GSNO). This suggests that GSNO killing of C. difficile contributes to its efficacy in murine CDI. Although nitric oxide production could not be detected for the nitroheterocyclic drugs, the cellular response to metronidazole and nitrofurans has some overlap with the response to GSNO, causing significant upregulation of the hybrid-cluster protein Hcp that responds to nitrosative stress. These findings provide new insights into the action of nitroheterocyclic drugs against C. difficile.

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Section: Discussionmentioning

confidence: 54%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Action of nitroheterocyclic drugs against Clostridium difficile

Kumar

Adhikari

Hurdle

2014

International Journal of Antimicrobial Agents

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“…This leads to inhibition of the peptidyl transferase activity and prevention of protein chain elongation (Wolfe and Hahn, 1965;Greenwood and Whitley, 2002;Anderson et al, 2012). The binding of chloramphenicol to the peptidyl transferase centre A is highly specific and reversible, illustrating its bacteriostatic nature.…”

Section: Modes Of Actionmentioning

confidence: 99%

Scientific Opinion on Chloramphenicol in food and feed

2014

EFS2

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Chloramphenicol is an antibiotic not authorised for use in food-producing animals in the European Union (EU). However, being produced by soil bacteria, it may occur in plants. The European Commission asked EFSA for a scientific opinion on the risks to human and animal health related to the presence of chloramphenicol in food and feed and whether a reference point for action (RPA) of 0.3 µg/kg is adequate to protect public and animal health. Data on occurrence of chloramphenicol in food extracted from the national residue monitoring plan results and from the Rapid Alert System for Food and Feed (RASFF) were too limited to carry out a reliable human dietary exposure assessment. Instead, human dietary exposure was calculated for a scenario in which chloramphenicol is present at 0.3 µg/kg in all foods of animal origin, foods containing enzyme preparations and foods which may be contaminated naturally. The mean chronic dietary exposure for this worst-case scenario would range from 11 to 17 and 2.2 to 4.0 ng/kg b.w. per day for toddlers and adults, respectively. The potential dietary exposure of livestock to chloramphenicol was estimated to be below 1 µg/kg b.w. per day. Chloramphenicol is implicated in the generation of aplastic anaemia in humans and causes reproductive/hepatotoxic effects in animals. Margins of exposure for these effects were calculated at 2.4 × 10 5 or greater and the CONTAM Panel concluded that it is unlikely that exposure to food contaminated with chloramphenicol at or below 0.3 µg/kg is a health concern for aplastic anaemia or reproductive/hepatotoxic effects. Chloramphenicol exhibits genotoxicity but, owing to the lack of data, the risk of carcinogenicity cannot be assessed. The SUMMARYChloramphenicol is a broad-spectrum antibiotic effective against Gram-positive and Gram-negative bacteria and, in the past, has been widely used to treat infections in both humans and animals. Chloramphenicol is not authorised for use in food-producing animals in the European Union (EU) but may be used in human medicine and in treatments for non-food-producing animals. Apart from its potential occurrence as a residue in food from illicit treatment of food-producing animals, chloramphenicol has also been used in feed and food enzyme products and may occur naturally in plants from its production by the soil bacterium Streptomyces venezuelae.The EFSA Scientific Opinion entitled "Guidance on methodological principles and scientific methods to be taken into account when establishing Reference Points for Action (RPAs) for non-allowed pharmacologically active substances present in food of animal origin" identified an approach for establishing RPAs for various categories of non-allowed pharmacologically active substances. However, the opinion also identified certain categories of non-allowed pharmacologically active substances that are considered to be outside the scope of the procedure, including substances causing blood dyscrasias (aplastic anaemia) such as chloramphenicol. As chloramphenicol is excluded fro...

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Bio‐Organometallic Derivatives of Antibacterial Drugs

Sierra

Casarrubios

Torre

2019

Chemistry A European J

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Overuse and misuse of antibacterial drugs has resulted in bacteria resistance and in an increase in mortality rates due to bacterial infections. Therefore, there is an imperative necessity of new antibacterial drugs. Bio-organometallic derivatives of antibacterial agents offer an opportunity to discover new active antibacterial drugs. These compounds are well-characterized products and, in several examples, their antibacterial activities have been studied. Both inhibition of the antibacterial activity and strong increase in the antibiotic activity of the parent drug have been found. The synthesis of the main classes of bio-organometallic derivatives of these drugs, as well as examples of the use of structure-activity relation&&Ok?&& (SAR) studies to increase the activity and to understand the mode of action of bio-organometallic antimicrobial peptides (BOAMPs) and platensimicyn bio-organometallic mimics is presented in this article.

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Antibacterial Agents

Cited by 73 publications

References 0 publications

Action of nitroheterocyclic drugs against Clostridium difficile

Action of nitroheterocyclic drugs against Clostridium difficile

Scientific Opinion on Chloramphenicol in food and feed

Bio‐Organometallic Derivatives of Antibacterial Drugs

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