ChemInform Abstract: Branched and Chain‐Extended Sugars. Part 31. Synthesis of the Deferri Form of the Oxygen Analogue of δ1‐Albomycin.

Paulsen, Hans; Brieden, M.; Benz, G.

doi:10.1002/chin.198743350

Cited by 4 publications

(4 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Albomycin links a thioribosyl-pyrimidine moiety to the ferrichrome siderophore (Figure 1), which is efficiently released in the bacterial cytoplasm to inhibit seryl t-RNA synthetase, shutting down bacterial protein synthesis. [8][9][10] Albomycin is active against numerous Gram-negative strains and has been utilized effectively as an antibiotic in mammals, with isolation from bacterial culture as the primary source; recently, the total synthesis of albomycin has been reported. 11 Another prominent natural product of the siderophore-antibiotic (sideromycin) family is salmycin.…”

Section: Introductionmentioning

confidence: 99%

Theranostic Gallium Siderophore Ciprofloxacin Conjugate with Broad Spectrum Antibiotic Potency

et al. 2019

View full text Add to dashboard Cite

Pathogenic bacteria scavenge ferric iron from the host for survival and proliferation using smallmolecular chelators, siderophores. Here, we introduce and assess the gallium(III) complex of ciprofloxacin-functionalized desferrichrome (D2) as a potential therapeutic for bacterial infection using an in vitro assay and radiochemical, tracer-based approach. Ga-D2 exhibits a minimum inhibitory concentration of 0.23 μM in Escherichia coli, in line with the parent fluoroquinolone antibiotic. Competitive and mutant strain assays show that Ga-D2 relies on FhuA-mediated transport for internalization. Ga-D2 is potent against Pseudomonas aeruginosa (3.8 μM), Staphylococcus aureus (0.94 μM), and Klebsiella pneumoniae (12.5 μM), while Fe-D2 is inactive in these strains. Radiochemical experiments with E. coli reveal that 67 Ga-D2 is taken up more efficiently than 67 Ga-citrate. In naive mice, 67 Ga-D2 clears renally and is excreted 13% intact in the urine. These pharmacokinetic and bacterial growth inhibitory properties qualify Ga-D2 for future investigations as a diagnosis and treatment tool for infection.

show abstract

Section: Introductionmentioning

confidence: 99%

Theranostic Gallium Siderophore Ciprofloxacin Conjugate with Broad Spectrum Antibiotic Potency

et al. 2019

View full text Add to dashboard Cite

show abstract

“…However, no total synthesis of albomycins has been reported. In one study 22 , an oxygen analog of 1a was synthesized. Surprisingly, a single replacement of the sulfur with oxygen resulted in the complete loss of antibacterial activity, suggesting a critical role of the sulfur atom in the activity of albomycins.…”

Section: Introductionmentioning

confidence: 99%

Total synthesis and antimicrobial evaluation of natural albomycins against clinical pathogens

Lin

Zhao

et al. 2018

Nat Commun

View full text Add to dashboard Cite

Development of effective antimicrobial agents continues to be a great challenge, particularly due to the increasing resistance of superbugs and frequent hospital breakouts. There is an urgent need for more potent and safer antibiotics with novel scaffolds. As historically many commercial drugs were derived from natural products, discovery of antimicrobial agents from complex natural product structures still holds a great promise. Herein, we report the total synthesis of natural albomycins δ1 (1a), δ2 (1b), and ε (1c), which validates the structures of these peptidylnucleoside compounds and allows for synthetic access to bioactive albomycin analogs. The efficient synthesis of albomycins enables extensive evaluations of these natural products against model bacteria and clinical pathogens. Albomycin δ2 has the potential to be developed into an antibacterial drug to treat Streptococcus pneumoniae and Staphylococcus aureus infections.

show abstract

“…Compound 10 , on the contrary, exhibited the most potent activity against the Gram-negative bacteria Neisseria gonorrhoeae (MIC = 0.0039 μg/mL), while for compound 12 no antibacterial activity was detected . A thiolane moiety seems to be required for antibacterial activity, since an analogue of compound 10 in which the sulfur atom was substituted by an oxygen atom did not yield any antibacterial activity. , …”

Section: Siderophore–antibiotic Conjugatesmentioning

confidence: 94%

Emerging Target-Directed Approaches for the Treatment and Diagnosis of Microbial Infections

et al. 2022

View full text Add to dashboard Cite

With the rising levels of drug resistance, developing efficient antimicrobial therapies has become a priority. A promising strategy is the conjugation of antibiotics with relevant moieties that can potentiate their activity by target-directing. The conjugation of siderophores with antibiotics allows them to act as Trojan horses by hijacking the microorganisms' highly developed iron transport systems and using them to carry the antibiotic into the cell. Through the analysis of relevant examples of the past decade, this Perspective aims to reveal the potential of siderophore−antibiotic Trojan horses for the treatment of infections and the role of siderophores in diagnostic techniques. Other conjugated molecules will be the subject of discussion, namely those involving vitamin B12, carbohydrates, and amino acids, as well as conjugated compounds targeting protein degradation and β-lactamase activated prodrugs.

show abstract

ChemInform Abstract: Branched and Chain‐Extended Sugars. Part 31. Synthesis of the Deferri Form of the Oxygen Analogue of δ1‐Albomycin.

Cited by 4 publications

References 1 publication

Theranostic Gallium Siderophore Ciprofloxacin Conjugate with Broad Spectrum Antibiotic Potency

Theranostic Gallium Siderophore Ciprofloxacin Conjugate with Broad Spectrum Antibiotic Potency

Total synthesis and antimicrobial evaluation of natural albomycins against clinical pathogens

Emerging Target-Directed Approaches for the Treatment and Diagnosis of Microbial Infections

Contact Info

Product

Resources

About