Acid catalysed degradation of some spiramycin derivatives found in the antibiotic bitespiramycin

Shi, Xiangguo; Zhang, Shuqiu; Fawcett, J. Paul; Zhong, Dafang

doi:10.1016/j.jpba.2004.07.037

Cited by 16 publications

(5 citation statements)

References 12 publications

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“…These metabolites (platenomycin A1, josamycin, leucomycin A1 and midecamycin) were produced by loss of forosamine from the corresponding constituents of bitespiramycin. This represents a novel metabolic pathway for spiramycin derivatives (Shi et al 2004b). The identification of the reduced metabolites of bitespiramycin in feces (M3 and M7 series) represents another novel biotransformation pathway for spiramycin derivatives, which were found only in feces and therefore most probably derived from gut microfloral metabolism.…”

Section: Discussionmentioning

confidence: 97%

Structural identification of bitespiramycin metabolites in rat: A single oral dose study

et al. 2005

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Bitespiramycin is a macrolide antibiotic consisting of a mixture of some nine spiramycin ester derivatives. It has a similar spectrum of antibiotic activity to that of spiramycin but has superior pharmacokinetic properties. In this study, a rapid and facile LC/ESI-MSn method was applied to study the metabolism of bitespiramycin in rat following a single oral dose (80 mg kg-1). Concentrations of parent drug constituents and metabolites were determined in plasma, urine, feces and bile. Concentrations of parent drug constituents and metabolites in plasma were very low. In urine, feces and bile, parent drug constituents and 38 metabolites were identified on the basis of their chromatographic and mass spectrometric properties. The identity of 17 metabolites was confirmed by comparison with reference substances. The principal metabolites were the corresponding spiramycins formed by hydrolysis of the 4''-(3-methylbutanoate) groups. Other important metabolic pathways were: hydrolytic loss of the forosamine and mycarose sugars; aldehyde reduction; cysteine conjugation of the aldehyde group; and hydrolysis of the lactone ring. Products formed by lactone ring opening were found only in urine, and those formed by aldehyde reduction were found only in feces. Aldehyde reduction and hydrolytic loss of forosamine represent novel biotransformation pathways for spiramycin derivatives.

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Section: Discussionmentioning

confidence: 97%

Structural identification of bitespiramycin metabolites in rat: A single oral dose study

et al. 2005

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“…The pK a of SPM is 7.71. Further, SPM is stable at pH values from 4 to 10 below 60 • C [39]. Spiramycin presented a great capacity to distribute to the EOPO-rich phase in both EO 20 PO 80 ATPS and EO 30 PO 70 ATPS (Figure 5).…”

Section: Spiramycin Partitionmentioning

confidence: 99%

Effective extraction of tylosin and spiramycin from fermentation broth using thermo‐responsive ethylene oxide/propylene oxide aqueous two‐phase systems

Yang

Zheng

Yan

et al. 2021

J of Separation Science

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Recyclable aqueous two-phase systems with thermo-responsive phase-forming materials have been employed to separate macromolecules; however, these systems have achieved very limited separation efficiency for small molecules, such as antibiotics. In this study, aqueous two-phase systems composed of the ethylene oxide/propylene oxide copolymer and water were developed to extract alkaline antibiotics from the fermentation broth. In the aqueous twophase systems with an ethylene oxide ratio of 20 and propylene oxide ratio of 80, the partition coefficients of tylosin and spiramycin reached 16.87 and 20.39, respectively, while the extraction recoveries were 70.67 and 86.70%, respectively. Coupled with mechanism analysis, we demonstrated the feasibility of extracting alkaline antibiotics using this aqueous two-phase system, especially for 16-membered macrolide antibiotics. The molecular dynamic simulation was employed to visualize the process of dual-phase formation and the partition behavior of antibiotics in an aqueous two-phase system. The dynamic simulation revealed the binding energy between the antibiotic and ethylene oxide/propylene oxide copolymers, which provides a simple indicator for screening suitable antibiotics in aqueous two-phase systems. Our recyclable aqueous two-phase systems provide a robust approach for the extraction of 16-membered macrolide antibiotics with ease of operation and high recovery rates, which is appropriate for large-scale extraction in the fermentation industry.

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“…Spiramycin, a 16-membered macrolide antibacterial agent, can be transformed into neospiramycin by losing a mycarose group, which can be further transformed into forocidin by losing a forosamine group through hydrolysis. 35,36 Some minor spiramycin-related substances such as methylenespiramycin and deoxydihydrospiramycin have also been reported. 37 Among these substances, neospiramycin was identied as the major transformation product of spiramycin 32,38 reaching up to 5.3 AE 0.4 mg L À1 in spiramycin production wastewater.…”

Section: Assessment Of Transformation Product Contributions To Wastew...mentioning

confidence: 99%

Evaluation of residual antibacterial potency in antibiotic production wastewater using a real-time quantitative method

Zhang

Yang

Liu

2015

Environ. Sci.: Processes Impacts

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a While antibiotic pollution has attracted considerable attention due to its potential in promoting the dissemination of antibiotic resistance genes in the environment, the antibiotic activity of their related substances has been neglected, which may underestimate the environmental impacts of antibiotic wastewater discharge. In this study, a real-time quantitative approach was established to evaluate the residual antibacterial potency of antibiotics and related substances in antibiotic production wastewater (APW) by comparing the growth of a standard bacterial strain (Staphylococcus aureus) in tested water samples with a standard reference substance (e.g. oxytetracycline). Antibiotic equivalent quantity (EQ) was used to express antibacterial potency, which made it possible to assess the contribution of each compound to the antibiotic activity in APW. The real-time quantitative method showed better repeatability (Relative Standard Deviation, RSD 1.08%) compared with the conventional fixed growth time method (RSD 5.62-11.29%). And its quantification limits ranged from 0.20 to 24.00 mg L À1, depending on the antibiotic. We applied the developed method to analyze the residual potency of water samples from four APW treatment systems, and confirmed a significant contribution from antibiotic transformation products to potent antibacterial activity. Specifically, neospiramycin, a major transformation product of spiramycin, was found to contribute 13.15-22.89% of residual potency in spiramycin production wastewater. In addition, some unknown related substances with antimicrobial activity were indicated in the effluent. This developed approach will be effective for the management of antibacterial potency discharge from antibiotic wastewater and other waste streams. Environmental impactAntibiotic pollution from antibiotic production wastewater has caused increasing concern worldwide. Previous studies have focused on the discharge of antibiotics by determining their concentrations. However, some antibiotic related substances in effluents still possess antibacterial activity, which might induce emergence and proliferation of antibiotic resistant bacteria and genes in the environment. Therefore, it is important to investigate residual antibacterial potency in antibiotic production wastewater with high concentrations of antibiotics and related substances. In this study, a real-time quantitative method was developed and applied for the analysis of residual antibacterial potency of antibiotic production wastewater. The results showed that spiramycin production wastewater contained transformation products with high potency. This method made it possible to assess the contribution of each compound and should be a useful tool for environmental risk management for providing the basis for identication of transformation products with antibacterial activity.

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Acid catalysed degradation of some spiramycin derivatives found in the antibiotic bitespiramycin

Cited by 16 publications

References 12 publications

Structural identification of bitespiramycin metabolites in rat: A single oral dose study

Structural identification of bitespiramycin metabolites in rat: A single oral dose study

Effective extraction of tylosin and spiramycin from fermentation broth using thermo‐responsive ethylene oxide/propylene oxide aqueous two‐phase systems

Evaluation of residual antibacterial potency in antibiotic production wastewater using a real-time quantitative method

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