Source:http://linkedlifedata.com/resource/pubmed/id/16302813
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rdf:type | |
lifeskim:mentions |
umls-concept:C0003392,
umls-concept:C0064693,
umls-concept:C0205314,
umls-concept:C0220781,
umls-concept:C0243071,
umls-concept:C0596402,
umls-concept:C0600115,
umls-concept:C0679622,
umls-concept:C1136197,
umls-concept:C1516769,
umls-concept:C1533691,
umls-concept:C1880157,
umls-concept:C1883254,
umls-concept:C2603343
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pubmed:issue |
24
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pubmed:dateCreated |
2005-11-23
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pubmed:abstractText |
Novel lavendamycin analogues with various substituents were synthesized and evaluated as potential NAD(P)H:quinone oxidoreductase (NQO1)-directed antitumor agents. Pictet-Spengler condensation of quinoline- or quninoline-5,8-dione aldehydes with tryptamine or tryptophans yielded the lavendamycins. Metabolism studies with recombinant human NQO1 revealed that addition of NH2 and CH2OH groups at the quinolinedione-7-position and indolopyridine-2'-position had the greatest positive impact on substrate specificity. The best and poorest substrates were 37 (2'-CH2OH-7-NH2 derivative) and 31 (2'-CONH2-7-NHCOC3H7-n derivative) with reduction rates of 263 +/- 30 and 0.1 +/- 0.1 micromol/min/mg NQO1, respectively. Cytotoxicity toward human colon adenocarcinoma cells was determined for the lavendamycins. The best substrates for NQO1 were also the most selectively toxic to the NQO1-rich BE-NQ cells compared to NQO1-deficient BE-WT cells with 37 as the most selective. Molecular docking supported a model in which the best substrates were capable of efficient hydrogen-bonding interactions with key residues of the active site along with hydride ion reception.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0022-2623
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pubmed:author |
pubmed-author:BeallHoward DHD,
pubmed-author:BehforouzMohammadM,
pubmed-author:EbrahimianG RezaGR,
pubmed-author:GerdesJohn MJM,
pubmed-author:HassaniMaryM,
pubmed-author:HolleyDavid CDC,
pubmed-author:LineswalaJayana PJP,
pubmed-author:MaharjanBabu RBR,
pubmed-author:MarvinChristopher CCC,
pubmed-author:MohammadiFarahnazF,
pubmed-author:SeradjHassanH,
pubmed-author:StocksdaleMark GMG,
pubmed-author:YanG FGF
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
48
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7733-49
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:16302813-Antineoplastic Agents,
pubmed-meshheading:16302813-Binding Sites,
pubmed-meshheading:16302813-Cell Line, Tumor,
pubmed-meshheading:16302813-Drug Screening Assays, Antitumor,
pubmed-meshheading:16302813-Electrochemistry,
pubmed-meshheading:16302813-Humans,
pubmed-meshheading:16302813-Hydrogen Bonding,
pubmed-meshheading:16302813-Models, Molecular,
pubmed-meshheading:16302813-NAD(P)H Dehydrogenase (Quinone),
pubmed-meshheading:16302813-Oxidation-Reduction,
pubmed-meshheading:16302813-Streptonigrin,
pubmed-meshheading:16302813-Structure-Activity Relationship
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pubmed:year |
2005
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pubmed:articleTitle |
Novel lavendamycin analogues as antitumor agents: synthesis, in vitro cytotoxicity, structure-metabolism, and computational molecular modeling studies with NAD(P)H:quinone oxidoreductase 1.
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pubmed:affiliation |
Department of Chemistry, Ball State University, Muncie, Indiana 47306, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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