A macromolecular prodrug of doxorubicin conjugated to a biodegradable cyclotriphosphazene bearing a tetrapeptide.

Abstract

A new biodegradable water-soluble phosphazene trimer-doxorubicin conjugate was synthesized, in which equimolar hydrophilic methoxy-poly(ethylene glycol) with a molecular weight of 350 (MPEG350) and a tumor-specific tetrapeptide (Gly-Phe-Leu-Gly) were grafted to cyclotriphosphazene. The present conjugate exhibited cytotoxicity lower than that of free doxorubicin (IC50=0.10 microM) but a reasonably higher in vitro cytotoxicity (IC50=1.1 microM) against the leukemia L1210 cell line probably due to its enzymatically controlled release.

• Authors: Jin Kyu Kim, Udaya S Toti, Rita Song, Youn Soo Sohn
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 15 Issue 15 Pg. 3576-9 (Aug 01 2005) ISSN: 0960-894X [Print] England
• PMID: 15982876 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibiotics, Antineoplastic
• Gly-Phe-Leu-Gly
• Nitriles
• Oligopeptides
• Phosphorus Compounds
• Prodrugs
• cyclotriphosphazene ester
• Polyethylene Glycols
• Doxorubicin

Topics

• Animals
• Antibiotics, Antineoplastic (chemical synthesis, pharmacology)
• Biodegradation, Environmental
• Cell Line, Tumor
• Doxorubicin (chemistry, pharmacology)
• Inhibitory Concentration 50
• Leukemia L1210 (drug therapy, pathology)
• Magnetic Resonance Spectroscopy
• Molecular Weight
• Nitriles (chemistry, pharmacology)
• Oligopeptides (chemical synthesis, chemistry, pharmacology)
• Phosphorus Compounds (chemistry, pharmacology)
• Polyethylene Glycols (chemistry, pharmacology)
• Prodrugs
• Stereoisomerism