Penicillin degradation catalysed by Zn(II) ions in methanol

Navarro, Pilar; Blázquez, Iluminada Hernández; Osso, Bartolomé Quintero; Parras, P. J. Martinez De Las; Puentedura, María I. Martínez; García, Álvarez

doi:10.1016/s0141-8130(03)00081-3

Cited by 44 publications

(29 citation statements)

References 15 publications

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“…The pK a of an aliphatic hydroxyl is on the order of 16 (value for ethanol) (19), indicating that acylation is unlikely to occur at a significant rate at physiological pH in the absence of a catalyst, and, accordingly, the cyclodipeptide cSer-Asn did not react with any of the ␤-lactams used in this study (data not shown). Of note, methanolysis of amoxicillin has been reported, but the initial rate was very low (8 ϫ 10 Ϫ8 M Ϫ1 min Ϫ1 ) (20). For sulfhydryl, the pK a is much lower, 9.24 Ϯ 0.01, as determined for the cyclic dipeptide cCys-Asn (Fig.…”

Section: Resultsmentioning

confidence: 76%

Negative Impact of Carbapenem Methylation on the Reactivity of β-Lactams for Cysteine Acylation as Revealed by Quantum Calculations and Kinetic Analyses

Bhattacharjee

Triboulet

Dubée

et al. 2019

Antimicrob Agents Chemother

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The Enterococcus faecium L,D-transpeptidase (Ldt fm ) mediates resistance to most ␤-lactam antibiotics in this bacterium by replacing classical peptidoglycan polymerases. The catalytic Cys of Ldt fm is rapidly acylated by ␤-lactams belonging to the carbapenem class but not by penams or cephems. We previously reported quantum calculations and kinetic analyses for Ldt fm and showed that the inactivation profile is not determined by differences in drug binding (K D [equilibrium dissociation constant] values in the 50 to 80 mM range). In this study, we analyzed the reaction of a Cys sulfhydryl with various ␤-lactams in the absence of the enzyme environment in order to compare the intrinsic reactivity of drugs belonging to the penam, cephem, and carbapenem classes. For this purpose, we synthesized cyclic Cys-Asn (cCys-Asn) to generate a soluble molecule with a sulfhydryl closely mimicking a cysteine in a polypeptide chain, thereby avoiding free reactive amino and carboxyl groups. Computational studies identified a thermodynamically favored pathway involving a concerted rupture of the ␤-lactam amide bond and formation of an amine anion. Energy barriers indicated that the drug reactivity was the highest for nonmethylated carbapenems, intermediate for methylated carbapenems and cephems, and the lowest for penams. Electron-withdrawing groups were key reactivity determinants by enabling delocalization of the negative charge of the amine anion. Acylation rates of cCys-Asn determined by spectrophotometry revealed the same order in the reactivity of ␤-lactams. We concluded that the rate of Ldt fm acylation is largely determined by the ␤-lactam reactivity with one exception, as the enzyme catalytic pocket fully compensated for the detrimental effect of carbapenem methylation.

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Section: Resultsmentioning

confidence: 76%

Negative Impact of Carbapenem Methylation on the Reactivity of β-Lactams for Cysteine Acylation as Revealed by Quantum Calculations and Kinetic Analyses

Bhattacharjee

Triboulet

Dubée

et al. 2019

Antimicrob Agents Chemother

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“…Other drugs (i.e. ampicillin, amoxicillin, penicillins V and G) degrade under the catalytic influence of transition metal cations41. Two GB nodes are placed here because they are metal chelators: deferasirox for iron and penicillamine for copper24; their GB modularity class mirrors the platelet aggregation inhibitor effect4243.…”

Section: Resultsmentioning

confidence: 99%

Clustering drug-drug interaction networks with energy model layouts: community analysis and drug repurposing

Udrescu

Sbârcea

Topîrceanu

et al. 2016

Sci Rep

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Analyzing drug-drug interactions may unravel previously unknown drug action patterns, leading to the development of new drug discovery tools. We present a new approach to analyzing drug-drug interaction networks, based on clustering and topological community detection techniques that are specific to complex network science. Our methodology uncovers functional drug categories along with the intricate relationships between them. Using modularity-based and energy-model layout community detection algorithms, we link the network clusters to 9 relevant pharmacological properties. Out of the 1141 drugs from the DrugBank 4.1 database, our extensive literature survey and cross-checking with other databases such as Drugs.com, RxList, and DrugBank 4.3 confirm the predicted properties for 85% of the drugs. As such, we argue that network analysis offers a high-level grasp on a wide area of pharmacological aspects, indicating possible unaccounted interactions and missing pharmacological properties that can lead to drug repositioning for the 15% drugs which seem to be inconsistent with the predicted property. Also, by using network centralities, we can rank drugs according to their interaction potential for both simple and complex multi-pathology therapies. Moreover, our clustering approach can be extended for applications such as analyzing drug-target interactions or phenotyping patients in personalized medicine applications.

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“…As previously discussed, temperature and storage time can result in degradation of antibiotics. Degradation of β-lactams has also been shown in the presence of various metal ions, where the ions catalyze the inactivation of the hydrolytic opening of β-lactams (Navarro et al, 2003; Michnik et al, 2004; Alekseev et al, 2006). Electrochemical oxidation of raw milk with an initial concentration of oxytetracycline of 100 mg/mL has resulted in an 83% reduction of this drug after a 6-h treatment (Kitazono et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Multiresidue screening of milk withheld for sale at dairy farms in central New York State

Pereira

Siler

Warnick

2014

Journal of Dairy Science

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Many of the drugs commonly used in lactating dairy cows result in residues in the milk, prohibiting its sale for human consumption. Milk withheld for sale because of drug treatment or from cows with high somatic cell counts is commonly called “waste milk.” One-third of dairy farms in the United States use waste milk to feed preweaned dairy calves. Limited information is currently available on the effect of this practice on the selection and dissemination of antibiotic-resistant bacteria. Pooled waste milk samples were collected from 34 dairy farms in central New York State with the objective of detecting the presence and quantity of drug residues in these samples. Samples were collected and refrigerated using ice packs and then stored at 4°C upon arrival at the Cornell laboratory (Ithaca, NY). Screening for β-lactam, tetracycline, and sulfonamide residues in the milk was performed using commercial enzyme-linked receptor-binding assay (SNAP) tests (Idexx Laboratories Inc., Westbrook, ME). Samples with a positive SNAP test were selected for screening using a multiresidue liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The SNAP tests revealed that 75, 14.3, and 7.1% of waste milk samples (n = 34) contained β-lactam, tetracycline, and sulfamethazine residues, respectively. Of the samples sent for LC-MS/MS (n = 28), half had detectable quantities of drug residues. The most prevalent drugs detected by LC-MS/MS were ceftiofur (39.2%; mean ± SE concentration = 0.151 ± 0.042 μg/mL), penicillin G (14.2%; mean ± SE concentration = 0.008 ± 0.001 μg/mL), and ampicillin (7.1%; mean ± SE concentration = 0.472 ± 0.43 μg/mL). In addition, one sample had detectable concentrations of oxytetracycline and one sample had detectable concentrations of sulfadimethoxine. These results provide insight on drug residues present in waste milk from select farm in upstate New York, and additionally indicate the need for additional studies targeting on-farm treatments that could degrade drug residues present in waste milk and reduce the potential effects on the biosphere from the disposal and use of waste milk as a feed source.

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Penicillin degradation catalysed by Zn(II) ions in methanol

Cited by 44 publications

References 15 publications

Negative Impact of Carbapenem Methylation on the Reactivity of β-Lactams for Cysteine Acylation as Revealed by Quantum Calculations and Kinetic Analyses

Negative Impact of Carbapenem Methylation on the Reactivity of β-Lactams for Cysteine Acylation as Revealed by Quantum Calculations and Kinetic Analyses

Clustering drug-drug interaction networks with energy model layouts: community analysis and drug repurposing

Multiresidue screening of milk withheld for sale at dairy farms in central New York State

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