Synthesis, stereochemical characterization, and antimicrobial evaluation of a potentially nonnephrotoxic 3′-C-acethydrazide puromycin analog
| Autor: | Blair A. Weaver, Amy R. Messersmith, Will E. Lynch, Josh Carter, Giuseppe Gumina, Maria A. Chiacchio, Brent D. Feske |
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| Rok vydání: | 2017 |
| Předmět: |
Staphylococcus aureus
medicine.drug_class Stereochemistry Antibiotics Chemistry Techniques Synthetic Microbial Sensitivity Tests Crystallography X-Ray 010402 general chemistry 01 natural sciences Biochemistry Nephrotoxicity Structure-Activity Relationship chemistry.chemical_compound Hydrolysis Staphylococcus epidermidis Drug Resistance Multiple Bacterial Amide Genetics medicine biology 010405 organic chemistry Stereoisomerism General Medicine Antimicrobial biology.organism_classification Anti-Bacterial Agents 0104 chemical sciences chemistry Puromycin Molecular Medicine Nucleoside |
| Zdroj: | Nucleosides, Nucleotides & Nucleic Acids. 36:224-241 |
| ISSN: | 1532-2335 1525-7770 |
| DOI: | 10.1080/15257770.2016.1264590 |
| Popis: | Puromycin is a peptidyl nucleoside endowed with significant antibiotic and anticancer properties, but also with an unfortunate nephrotoxic character that has hampered its use as a chemotherapeutic agent. Since hydrolysis of puromycin's amide to puromycin aminonucleoside is the first metabolic step leading to nephrotoxicity, we designed a 3′-C-hydrazide analog where the nitrogen and carbon functionality around the amide carbonyl of puromycin are inverted. The title compound, synthesized in 11 steps from D-xylose, cannot be metabolized to the nephrotoxic aminonucleoside. Evaluation of the title compound on Staphylococcus epidermidis and multi-drug resistance Staphylococcus aureus did not show significant antimicrobial activity up to a 400 μM concentration. |
| Databáze: | OpenAIRE |
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