Synthesis and Antibacterial Activity of Aminoalkylamides of Eremomycin

Moiseenko, Elena I.; Grammatikova, Natalia E.; Shchekotikhin, Andrey E.

doi:10.6060/mhc200812s

Cited by 2 publications

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References 14 publications

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“…Therefore, one of the current directions of our studies focused on finding new drugcandidates for the development of new semi-synthetic glycopeptides [2,7,18,19]. Particular attention is given to derivatives of the original antibiotic of this group, eremomycin, which was discovered by G.F. Gause et al [3,20].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Toxic Properties of New Glycopeptide Flavancin on Rats

et al. 2022

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Glycopeptide antibiotics have side effects that limit their clinical use. In view of this, the development of glycopeptides with improved chemotherapeutic properties remains the main direction in the search for new antibacterial drugs. The objective of this study was to evaluate the toxicological characteristics of new semi-synthetic glycopeptide flavancin. Acute and chronic toxicity of antibiotic was evaluated in Wistar rats. The medium lethal dose (LD50) and the maximum tolerated doses (MTD) were calculated by the method of Litchfield and Wilcoxon. In the chronic toxicity study, the treatment regimen consisted of 15 daily intraperitoneal injections using two dosage levels: 6 and 10 mg/kg/day. Total doses were equivalent to MTD or LD50 of flavancin, respectively. The study included assessment of the body weight, hematological parameters, blood biochemical parameters, urinalysis, and pathomorphological evaluation of the internal organs. The results of the study demonstrated that no clinical-laboratory signs of toxicity were found after 15 daily injections of flavancin at a total dose close to the MTD or LD50. The pathomorphological study did not reveal any lesions on the organ structure of animals after low-dose administration of flavancin. Thus, flavancin favorably differs in terms of toxicological properties from the glycopeptides currently used in the clinic.

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Section: Discussionmentioning

confidence: 99%

Evaluation of Toxic Properties of New Glycopeptide Flavancin on Rats

et al. 2022

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Aminoalkylamides of Eremomycin Exhibit an Improved Antibacterial Activity

et al. 2021

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After decades, the glycopeptide vancomycin is still the preferred antibiotic against resistant strains of Gram-positive bacteria. Although its clinical use is strictly regulated, the gradual spread of vancomycin-resistant bacteria, such as glycopeptide-resistant and glycopeptide-intermediate Staphylococcus aureus and vancomycin-resistant Enterococcus spp., is a serious health problem. Based on the literature data and previous studies, our main goal was to assess the antimicrobial potential and to study the structure–activity relationship of new eremomycin aminoalkylamides. We designed and synthesized a series of new eremomycin amides in which eremomycin is conjugated with a hydrophobic arylalkyl group via an alkylenediamine spacer, and tested their antibacterial activities on a panel of Gram-positive strains that were sensitive and resistant to a “gold-standard” vancomycin. Based on the data obtained, the structure–activity relationships were investigated, and a lead compound was selected for in-depth testing. Research carried out using an in vivo model of staphylococcus sepsis, acute toxicity studies, and the estimated therapeutic index also showed the advantage of the selected eremomycin amide derivative in particular, as well as the chosen direction in general.

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Synthesis and Antibacterial Activity of Aminoalkylamides of Eremomycin

Cited by 2 publications

References 14 publications

Evaluation of Toxic Properties of New Glycopeptide Flavancin on Rats

Evaluation of Toxic Properties of New Glycopeptide Flavancin on Rats

Aminoalkylamides of Eremomycin Exhibit an Improved Antibacterial Activity

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