title: Synthesis, stereochemical characterization, and antimicrobial evaluation of a potentially nonnephrotoxic 3'-C-acethydrazide puromycin analog.
abstract: 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.
authors.affiliation: a Department of Pharmaceutical and Administrative Sciences , Presbyterian College School of Pharmacy , Clinton , SC , USA.
authors.forename: Josh
authors.initials: J
authors.lastname: Carter
authors.affiliation: b Department of Chemistry and Physics , Armstrong State University , Savannah , GA , USA.
authors.forename: Blair A
authors.initials: BA
authors.lastname: Weaver
authors.affiliation: c Dipartimento di Scienze del Farmaco , Università di Catania , Catania , Italy.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Chiacchio
authors.affiliation: a Department of Pharmaceutical and Administrative Sciences , Presbyterian College School of Pharmacy , Clinton , SC , USA.
authors.forename: Amy R
authors.initials: AR
authors.lastname: Messersmith
authors.affiliation: b Department of Chemistry and Physics , Armstrong State University , Savannah , GA , USA.
authors.forename: Will E
authors.initials: WE
authors.lastname: Lynch
authors.affiliation: b Department of Chemistry and Physics , Armstrong State University , Savannah , GA , USA.
authors.forename: Brent D
authors.initials: BD
authors.lastname: Feske
authors.affiliation: a Department of Pharmaceutical and Administrative Sciences , Presbyterian College School of Pharmacy , Clinton , SC , USA.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gumina
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D018360:Crystallography, X-Ray; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D011691:Puromycin / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects; D013212:Staphylococcus epidermidis / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D011691:Puromycin
keywords: 3'-C-Nucleoside; Horner-Wadsworth-Emmons olefination; Puromycin; antibacterial