Metabolically Stable, Non-Nephrotoxic Puromycin Analogs as Oncology and Anti-infective Therapeutics
Medical University of South Carolina
posted on 03/28/2011
The synthesized compounds are novel analogs of Puromycin that have maintained the same antimicrobial and antitumor activities of the naturally occurring form, but block the formation of toxic by-products. These new analogs may provide promising chemotherapeutic agents that have the same effectiveness of Puromycin without the nephrotoxicity. In preliminary studies, the target compound showed cytotoxicity in breast cancer and leukemia cell lines at levels comparable to Puromycin.
Puromycin is a long-known antibiotic agent derived from the bacteria Streptomyces alboniger. By mimicking the 3'-end of aminoacyl-tRNA, Puromycin inhibits amino acid synthesis during translation. While Puromycin has clear scope for use as an antitumor agent, its metabolic conversion to Puromycin aminonucleoside (PAN) has potent, nephrotoxic side effects that have limited its potential for clinical use. To fully exploit Puromycin as an anticancer agent, it is necessary to develop a metabolically stable analog that retains the same antimicrobial and antitumor properties as the original compound, but lacks the nephrotoxicity.
Decreased nephrotoxicity with comparable cytotoxicity
Key Words: Cancer, antitumor agent, antibacterial, Puromycin
Publications: Gilbert, Carrie LK, et al. "Synthesis of l, l-puromycin." Tetrahedron 61.35 (2005): 8339-8344.
Inventors: G. Gumina, R. White
Patent Status: US Patent 7,897,759
MUSC-FRD Technology ID: P0709
File Number: P0709
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