Document Detail


Synthesis, NMR characterization and in vitro antitumor evaluation of new aminophosphonic acid diesters.
MedLine Citation:
PMID:  19361895     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The synthesis of three novel alpha-aminophosphonic acid diesters N,N-dimethyl-[N'-methyl(diethoxyphosphonyl)-(2-furyl)]-1,3-diaminopropane, p-[N-methyl(diethoxyphosphonyl)-(2-furyl)]toluidine and p-[N-methyl(diethoxyphosphonyl)-(4-dimethylaminophenyl)]toluidine through an addition of diethyl phosphite to N,N-dimethyl-N'-furfurylidene-1,3-diaminopropane, N-furfurylidene-p-toluidine and N-(4-dimethylaminobenzylidene)-p-toluidine, respectively, is reported. The alpha-aminophosphonates have been characterized by elemental analysis, IR and NMR ((1)H, (13)C and (31)P) spectra. The compounds were tested for antiproliferative effects against 4 human leukemic cell lines, namely LAMA-84, K-562 (chronic myeloid leukemias), HL-60 (acute promyelocyte leukemia) and HL-60/Dox (multi-drug-resistant sub-line, characterized by overexpression of MRP-1 (ABC-C1)) and were found to exert concentration-dependent cytotoxic effects. A representative aminophosphonate compound was shown to induce oligonucleosomal DNA fragmentation which implies that the induction of cell death through apoptosis plays an important role for its cytotoxicity mode of action.
Authors:
I Kraicheva; A Bogomilova; I Tsacheva; G Momekov; K Troev
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Publication Detail:
Type:  Journal Article     Date:  2009-03-24
Journal Detail:
Title:  European journal of medicinal chemistry     Volume:  44     ISSN:  1768-3254     ISO Abbreviation:  Eur J Med Chem     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-05-18     Completed Date:  2009-07-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0420510     Medline TA:  Eur J Med Chem     Country:  France    
Other Details:
Languages:  eng     Pagination:  3363-7     Citation Subset:  IM    
Affiliation:
Institute of Polymers, Bulgarian Academy of Sciences, Sofia, Bulgaria. kraicheva@yahoo.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / chemical synthesis,  chemistry*,  pharmacology*
Cell Line, Tumor
Cell Survival / drug effects
Drug Design*
Drug Resistance, Multiple
Drug Resistance, Neoplasm
Gene Expression Regulation, Neoplastic / drug effects
Humans
Inhibitory Concentration 50
Magnetic Resonance Spectroscopy
Multidrug Resistance-Associated Proteins / metabolism
Phosphonic Acids / chemical synthesis,  chemistry*,  pharmacology*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Multidrug Resistance-Associated Proteins; 0/Phosphonic Acids; 0/multidrug resistance-associated protein 1

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