Document Detail

Synthesis and uptake of fluorescence-labeled Combi-molecules by P-glycoprotein-proficient and -deficient uterine sarcoma cells MES-SA and MES-SA/DX5.
MedLine Citation:
PMID:  20151639     Owner:  NLM     Status:  MEDLINE    
Here, we report on the first synthesis of fluorescent-labeled epidermal growth factor receptor-DNA targeting combi-molecules, and we studied the influence of P-glycoprotein status of human sarcoma MES-SA cells on their growth inhibitory effect and cellular uptake. The results showed that 6, bearing a longer spacer between the quinazoline ring and the dansyl group, was more stable and more cytotoxic than 4. In contrast to the latter, it induced significant levels of DNA damage in human tumor cells. Moreover, in contrast to doxorubicin, a drug known to be actively effluxed by P-gp, the more stable combi-molecule 6 induced almost identical levels of drug uptake and DNA damage in P-gp-proficient and -deficient cells. Likewise, in contrast to doxorubicin, 4 and 6 exerted equal levels of antiproliferative activity against the two cell types. The results in toto suggest that despite their size, the antiproliferative effects of 4 and 6 were independent of P-gp status of the cells.
Anne-Laure Larroque-Lombard; Margarita Todorova; Nahid Golabi; Christopher Williams; Bertrand J Jean-Claude
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  53     ISSN:  1520-4804     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-04     Completed Date:  2010-04-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2104-13     Citation Subset:  IM    
Cancer Drug Research Laboratory, Department of Medicine, Division of Medical Oncology, McGill University Health Center/Royal Victoria Hospital, 687 Pine Avenue West Room M-719, Montreal, Quebec H3A 1A1, Canada.
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MeSH Terms
Antineoplastic Agents / chemical synthesis*,  chemistry,  pharmacokinetics
Cell Line, Tumor
Cell Proliferation / drug effects
Comet Assay
DNA / antagonists & inhibitors,  metabolism
DNA Damage
Dansyl Compounds / chemical synthesis*,  chemistry,  pharmacokinetics
Flow Cytometry
Magnetic Resonance Spectroscopy
Microscopy, Fluorescence
P-Glycoprotein / deficiency,  metabolism*
Quinazolines / chemical synthesis*,  chemistry,  pharmacokinetics
Receptor, Epidermal Growth Factor / antagonists & inhibitors,  metabolism
Sarcoma / metabolism*
Spectrometry, Mass, Electrospray Ionization
Structure-Activity Relationship
Uterine Neoplasms / metabolism*
Reg. No./Substance:
0/Antineoplastic Agents; 0/Dansyl Compounds; 0/P-Glycoprotein; 0/Quinazolines; 9007-49-2/DNA; EC, Epidermal Growth Factor

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

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