Document Detail


Correlation of the acid-sensitivity of polyethylene glycol daunorubicin conjugates with their in vitro antiproliferative activity.
MedLine Citation:
PMID:  16546396     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Polyethylene glycol conjugates with linkers of varying acid-sensitivity were prepared by reacting five maleimide derivatives of daunorubicin containing an amide bond (1) or acid-sensitive carboxylic hydrazone bonds (2-5) with alpha-methoxy-poly(ethylene glycol)-thiopropionic acid amide (MW 20000) or alpha,omega-bis-thiopropionic acid amide poly(ethylene glycol) (MW 20000). The polymer drug derivatives were designed to release daunorubicin inside the tumor cell by acid-cleavage of the hydrazone bond after uptake of the conjugate by endocytosis. In subsequent cell culture experiments, the order of antitumor activity of the PEG daunorubicin conjugates correlated with their acid-sensitivity as determined by HPLC (cell lines: BXF T24 bladder carcinoma and LXFL 529L lung cancer cell line; assay: propidium iodide fluorescence assay). The acid-sensitivity of the link between PEG and daunorubicin is therefore an important parameter for in vitro efficacy.
Authors:
Paula C A Rodrigues; Thomas Roth; Heinz H Fiebig; Clemens Unger; Rolf Mülhaupt; Felix Kratz
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-03-20
Journal Detail:
Title:  Bioorganic & medicinal chemistry     Volume:  14     ISSN:  0968-0896     ISO Abbreviation:  Bioorg. Med. Chem.     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-05-08     Completed Date:  2006-08-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9413298     Medline TA:  Bioorg Med Chem     Country:  England    
Other Details:
Languages:  eng     Pagination:  4110-7     Citation Subset:  IM    
Affiliation:
Tumor Biology Center, Department of Medical Oncology, Clinical Research, Breisacher Strasse 117, D-79106 Freiburg, Germany.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / chemical synthesis,  chemistry*,  pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects*
Daunorubicin / analogs & derivatives*,  chemistry,  pharmacology*
Drug Evaluation, Preclinical
Humans
Hydrogen-Ion Concentration
Molecular Conformation
Polyethylene Glycols / chemical synthesis,  chemistry*
Structure-Activity Relationship
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Polyethylene Glycols; 20830-81-3/Daunorubicin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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