Maleimide-oligo(ethylene glycol) Derivatives of Camptothecin as Albumin-Binding Prodrugs: Synthesis and Antitumor Efficacy
| Autor: | Felix Kratz, André Warnecke |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Magnetic Resonance Spectroscopy
Stereochemistry Carboxylic acid Transplantation Heterologous Biomedical Engineering Mice Nude Pharmaceutical Science Bioengineering High-performance liquid chromatography Maleimides Mice chemistry.chemical_compound medicine Animals Humans Prodrugs Maleimide Serum Albumin Pharmacology chemistry.chemical_classification Organic Chemistry Albumin Prodrug Antineoplastic Agents Phytogenic Cross-Linking Reagents chemistry Drug delivery Solvents Camptothecin Ethylene Glycols Female Indicators and Reagents Spectrophotometry Ultraviolet Colorectal Neoplasms Ethylene glycol Neoplasm Transplantation Protein Binding Biotechnology medicine.drug |
| Zdroj: | Bioconjugate Chemistry. 14:377-387 |
| ISSN: | 1520-4812 1043-1802 |
| DOI: | 10.1021/bc0256289 |
| Popis: | In situ binding of thiol-reactive prodrugs to the cysteine-34 position of circulating albumin is a new approach in drug delivery. Therefore, five maleimide-bearing derivatives of the anticancer drug camptothecin (CPT) were developed as albumin-binding prodrugs. These compounds were synthesized by reacting heterobifunctional cross-linkers based on oligo(ethylene glycols) [3-6 (O-CH(2)-CH(2)) units] bearing a maleimide group on one end and a carboxylic acid group on the other with camptothecin 20-O-glycinate. Incorporating oligo(ethylene glycol) chains into the prodrugs enhanced their water-solubility when compared to the parent compound (up to 27-fold). HPLC studies showed that the prodrugs react almost quantitatively with the cysteine-34 position of endogenous albumin within a few minutes after incubation of the CPT derivatives with human blood plasma. The therapeutic potential of two of the prodrugs was assessed in nude mice bearing a colon xenograft (HT-29). Both albumin-binding derivatives of camptothecin were well-tolerated and showed enhanced antitumor efficacy when compared to CPT. |
| Databáze: | OpenAIRE |
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