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Antifungal Activity of Gepinacin Scaffold Glycosylphosphatidylinositol Anchor Biosynthesis Inhibitors with Improved Metabolic Stability
- Source :
- Antimicrob Agents Chemother
- Publication Year :
- 2020
- Publisher :
- American Society for Microbiology, 2020.
-
Abstract
- The glycosylphosphatidylinositol anchor biosynthesis inhibitor gepinacin demonstrates broad-spectrum antifungal activity and negligible mammalian toxicity in culture but is metabolically labile. The stability and bioactivity of 39 analogs were tested in vitro to identify LCUT-8, a stabilized lead with increased potency and promising single-dose pharmacokinetics. Unfortunately, no antifungal activity was seen at the maximum dosing achievable in a neutropenic rabbit model. Nevertheless, structure-activity relationships identified here suggest strategies to further improve compound potency, solubility, and stability.
- Subjects :
- Antifungal
Scaffold
Antifungal Agents
Glycosylphosphatidylinositols
medicine.drug_class
Structure-Activity Relationship
03 medical and health sciences
chemistry.chemical_compound
Pharmacokinetics
Biosynthesis
medicine
Animals
Potency
Structure–activity relationship
Experimental Therapeutics
Pharmacology (medical)
Glycosylphosphatidylinositol anchor
030304 developmental biology
Pharmacology
0303 health sciences
030306 microbiology
Chemistry
In vitro
3. Good health
Infectious Diseases
Biochemistry
Rabbits
Subjects
Details
- ISSN :
- 10986596 and 00664804
- Volume :
- 64
- Database :
- OpenAIRE
- Journal :
- Antimicrobial Agents and Chemotherapy
- Accession number :
- edsair.doi.dedup.....df123af6b3205463ed5e4d759d766854