A new aminoglycoside antibiotic G-367 S1, 2'-N-formylsisomicin fermentation, isolation and characterization.

Satoi, Shūzō; Awata, Masashi; Muto, Naoki; Hayashi, Masahito; Sagai, Hitoshi; Otani, Motoyasu

doi:10.7164/antibiotics.36.1

Cited by 6 publications

(2 citation statements)

References 4 publications

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“…These observations on the influence of amide formation at the 2′-position are consistent with the prior literature describing other 2′-amides. Thus, it has been reported that the 2′- N -glycinamide derivatives of simple aminoalkyl 2,6-diamino-α- d -glucopyranosides, and of fortimicin B, retain antibacterial activity as does 2′-formamido sisomicin. − …”

Section: Resultsmentioning

confidence: 99%

Modification at the 2′-Position of the 4,5-Series of 2-Deoxystreptamine Aminoglycoside Antibiotics To Resist Aminoglycoside Modifying Enzymes and Increase Ribosomal Target Selectivity

et al. 2019

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A series of derivatives of the 4,5-disubstituted class of 2-deoxystreptamine aminoglycoside antibiotics neomycin, paromomycin, and ribostamycin have been prepared and assayed for i) their ability to inhibit protein synthesis by bacterial ribosomes and by engineered bacterial ribosomes carrying eukaryotic decoding A sites; ii) antibacterial activity against wild type Gram negative and positive pathogens, and iii) overcoming resistance due to the presence of aminoacyl transferases acting at the 2’-position. The presence of five suitably-positioned residual basic amino groups was found to be necessary for activity to be retained upon removal or alkylation of the 2’-position amine. As alkylation of the 2’-amino group overcomes the action of resistance determinants acting at that position and in addition results in increased selectivity for the prokaryotic over eukaryotic ribosomes, it constitutes an attractive modification for introduction into next generation aminoglycosides. In the neomycin series the installation of small (formamide) or basic (glycinamide) amido groups on the 2’-amino group is tolerated.

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Section: Resultsmentioning

confidence: 99%

Modification at the 2′-Position of the 4,5-Series of 2-Deoxystreptamine Aminoglycoside Antibiotics To Resist Aminoglycoside Modifying Enzymes and Increase Ribosomal Target Selectivity

et al. 2019

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“…4,5 To reduce the incidence of graft infection, the development of prosthetic grafts that are resistant to infection has been anticipated. [6][7][8] Sisomicin (SISO) is used for prevention of postoperative infections [9][10][11] because it shows excellent antibacterial activities not only against Pseudomonas aeruginosa but also against staphylococci, including Staphylococcus aureus and Staphylococcus epidermidis, two of the major causative bacteria in graft infection. Fibrin glue (FG), which was developed as a tissue adhesive, is used for prevention of bleeding and sutural insufficiency in surgery at various sites.…”

Section: Introductionmentioning

confidence: 99%

Distribution and serum concentration of sisomicin released from fibrin glue-sealed Dacron graft in the rat and human

Osada¹,

Yamamura²,

Yano³

et al. 2000

J. Biomed. Mater. Res.

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We investigated whether or not fibrin glue (FG) used as a sealant in vascular prostheses to prevent leakage might be useful as a carrier of antibiotics for the prevention of local graft infection. Sisomicin (SISO) was incorporated into fibrin glue (SISO-FG) and evaluated as to its safety and pharmacokinetics. SISO (1.75 mg) -FG Dacron grafts were implanted subcutaneously in the anterior abdominal region of Sprague-Dawley rats, and then the changes in SISO concentrations in the serum and in the tissue around the implantation sites were compared with those same sites in rats that had had intravenous injection of SISO (1.75 mg). The serum SISO concentrations were significantly lower in the SISO-FG Dacron graft group than they were in the intravenous injection group. However, until 4 h after implantation the SISO concentrations in the tissues around the implantation sites were significantly higher in the SISO-FG Dacron group than they were in the iv injection group, and the peak concentrations during that time were 5.8 times higher for the SISO-FG Dacron group than they were for the intravenous injection group. The ratio of the area under the tissue concentration time curve of SISO (AUC tissue) after implantation of the SISO-FG Dacron graft to that after intravenous injection of SISO was 13.08. Therefore, FG was considered to control the release of SISO into the serum and to maintain a high SISO concentration in the tissue around the implantation site. Clinically, SISO (45 mg) -FG was applied directly to the Dacron grafts implanted in 10 patients who underwent prosthetic vascular reconstruction. No graft infection was observed in any of the patients who received SISO-FG Dacron grafts. The mean serum concentration of SISO was 0.65+/-0.17 microg/mL after 1 h and 0.33+/- 0.21 microg/mL after 3 h. The results of these clinical applications are in close correlation with those of the animal experiment and suggest that FG is useful as a carrier of SISO, allowing its controlled release for the prevention of local infection.

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Aminoglycosides

Mcgregor

2000

Kirk-Othmer Encyclopedia of Chemical Technology

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Aminoglycosides are members of the class of antibacterial antibiotics, the structures of which are derived from D ‐streptamine, D ‐2‐deoxystreptamine, or closely related compounds. The term aminocyclitol is sometimes used to identify this group of compounds. In 1991, the most widely used aminoglycosides in medical practice were gentamicin, tobramycin, amikacin, and netilmicin. In general, the aminoglycosides are useful for the treatment of serious infections involving aerobic or facultative gram‐negative bacilli. The most common resistance mechanism involves the inactivation of the aminoglycoside by reactions catalyzed by plasmid‐borne enzymes. Less common resistance mechanisms include decreased affinity for the antibiotic by the bacterial ribosome and decreased rate of transport into the bacterial cytoplasm. The aminoglycosides are administered primarily by intravenous infusion or intramuscular injection. Most of the administered dose is eliminated unmetabolized in the urine. Potential toxicity is a primary limiting factor in the clinical use of aminoglycosides. The most important toxicities are nephrotoxicity, ototoxicity, and to a lesser extent, neuromuscular blockade. All the aminoglycosides in medical practice are capable of causing these adverse events. The effect of this potential is to prevent the use of significantly increased doses to cover difficult infections. The bactericidal mechanisms employed by aminoglycosides are incompletely understood. In the cytoplasm, ribosomal binding leads to misreading of the genetic code and production of abnormal proteins and protein synthesis inhibition. The cause of cell death is uncertain. A large amount of research has been conducted aimed at reducing the limitations in the areas of toxicity and susceptibility to bacterial resistance mechanisms while maintaining the advantages by modification of the aminoglycoside molecular structure. Overall, structural modification has been successful in reducing susceptibility to bacterial inactivation. It has not been possible, however, to substantially dissociate the toxicity potential from the antibacterial activity.

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A new aminoglycoside antibiotic G-367 S1, 2'-N-formylsisomicin fermentation, isolation and characterization.

Cited by 6 publications

References 4 publications

Modification at the 2′-Position of the 4,5-Series of 2-Deoxystreptamine Aminoglycoside Antibiotics To Resist Aminoglycoside Modifying Enzymes and Increase Ribosomal Target Selectivity

Modification at the 2′-Position of the 4,5-Series of 2-Deoxystreptamine Aminoglycoside Antibiotics To Resist Aminoglycoside Modifying Enzymes and Increase Ribosomal Target Selectivity

Distribution and serum concentration of sisomicin released from fibrin glue-sealed Dacron graft in the rat and human

Aminoglycosides

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