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Updated: Jul 13, 2026
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From a Natural Product to Its Biosynthetic Gene Cluster: A Demonstration Using Polyketomycin from Streptomyces diastatochromogenes Tü6028
Published on: January 13, 2017
Novel tethers in ketolide antibiotics.
Takushi Kaneko1, Karina Romero, Bryan Li
1Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA. takushikaneko@gmail.com
Bioorganic & Medicinal Chemistry Letters
|July 31, 2007
Summary
New macrolide antibiotics with stable linker groups were synthesized. These novel ketolides demonstrate strong activity against drug-resistant respiratory pathogens.
Area of Science:
- Medicinal Chemistry
- Organic Synthesis
- Pharmacology
Background:
- Macrolide antibiotics are crucial for treating bacterial infections.
- Emergence of macrolide-resistant pathogens necessitates development of new therapeutic agents.
- Existing macrolides face challenges with resistance and efficacy.
Purpose of the Study:
- To synthesize novel macrolide analogs with enhanced stability and activity.
- To investigate the structure-activity relationship (SAR) of new linker moieties.
- To evaluate the efficacy of synthesized compounds against resistant bacterial strains.
Main Methods:
- Utilized the Curtius rearrangement for synthesizing novel macrolide structures.
- Incorporated methylene units within carbamate and urea groups as linkers.
- Performed in vitro and in vivo assays to assess antimicrobial activity.
- Established the SAR for various heterocyclic components and linker designs.
Main Results:
- Successfully synthesized novel macrolide antibiotics containing specific linker groups.
- Demonstrated stability of the introduced linker units under physiological conditions.
- Achieved potent in vitro and in vivo activity against macrolide-resistant respiratory pathogens.
- Elucidated SAR trends, guiding future drug design.
Conclusions:
- The synthesized novel macrolides, or ketolides, exhibit promising antimicrobial properties.
- The stable linker strategy is effective in overcoming macrolide resistance.
- These findings offer a potential new class of antibiotics to combat resistant infections.
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