Synthesis, Stereochemical Characterization, and Antimicrobial Evaluation of a Potential Non-Nephrotoxic 3'-c-acethydrazide Puromycin Analog
Journal of Nucleosides, Nucleotides and Nucleic Acids
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.
Carter, Josh, Blair A. Weaver, Maria A. Chiacchio, Amy R. Messersmith, Will E. Lynch, Brent D. Feske, Giuseppe Gumina.
"Synthesis, Stereochemical Characterization, and Antimicrobial Evaluation of a Potential Non-Nephrotoxic 3'-c-acethydrazide Puromycin Analog."
Journal of Nucleosides, Nucleotides and Nucleic Acids, 36 (3): 224-241.