Document Detail

Beta-galactoside prodrugs of doxorubicin for application in antibody directed enzyme prodrug therapy/prodrug monotherapy.
MedLine Citation:
PMID:  17679550     Owner:  NLM     Status:  MEDLINE    
Anthracycline antibiotics, particularly doxorubicin and daunorubicin, have been used exten sively in the treatment of human malignancies. However cardiotoxicity and multidrug resistance are significant problems that limit the clinical efficacy of such agents. Rational design to avoid these side effects includes strategies such as drug targeting and prodrug synthesis. Described here are the synthesis and preliminary biological evaluation of the enzymatically activated two new prodrugs (6 & 11) of doxorubicin. These prodrugs were designed as potential candidates for selective chemotherapy in ADEPT or PMT strategies. They are constituted of a galactose moiety, a spacer and the cytotoxic drug and they differ by the type of spacer. The prodrugs were stable in a buffer, and the in vitro studies showed good detoxification and hydrolysis kinetics. As prodrug 11 was readily hydrolyzed, this could be a valuable candidate for further development.
HariKrishna Devalapally; Raghavendra Swamy Navath; Venkateshwarlu Yenamandra; RaghuRam Rao Akkinepally; Rama Krishna Devarakonda
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Archives of pharmacal research     Volume:  30     ISSN:  0253-6269     ISO Abbreviation:  Arch. Pharm. Res.     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-08-07     Completed Date:  2007-10-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8000036     Medline TA:  Arch Pharm Res     Country:  Korea (South)    
Other Details:
Languages:  eng     Pagination:  723-32     Citation Subset:  IM    
Drug Metabolism, Pharmacokinetics, Cancer & Aging Research Division, University College of Pharmaceutical Sciences, Kakatiya University, Warangal-9, AP, India.
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MeSH Terms
Antibodies / chemistry*
Cell Line, Tumor
Doxorubicin / analogs & derivatives*,  pharmacology*
Enzymes / chemistry*
Escherichia coli / enzymology
Galactosides / chemical synthesis*,  pharmacology*
Indicators and Reagents
Magnetic Resonance Spectroscopy
Prodrugs / chemical synthesis*,  pharmacology*
Spectrophotometry, Infrared
Spectrophotometry, Ultraviolet
beta-Galactosidase / metabolism
Reg. No./Substance:
0/Antibodies; 0/Buffers; 0/Enzymes; 0/Galactosides; 0/Indicators and Reagents; 0/Prodrugs; 0/Solutions; 0/beta-galactoside; 23214-92-8/Doxorubicin; EC

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