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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
2011-6-13
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pubmed:abstractText |
From the anti-tumor active N-tryptophanyl-?-carboline-3-carboxylic acid benzyl ester and ?-carboline-3-carbonyltryptophan benzyl ester, a pharmacophore, Trp-Trp-OBzl, was drawn. Based on the DOCK scores amino acid residue was inserted into the C-terminus of Trp-Trp-OBzl and twenty Trp-Trp-AA-OBzls (AA = amino acid residues) were provided as DNA intercalators. On the in vitro and in vivo models seventeen Trp-Trp-AA-OBzls were anti-tumor active, and twelve Trp-Trp-AA-OBzls were more active than cytarabine. In acute toxicity assay Trp-Trp-AA-OBzls did not damage the immunologic function and had an LD(50) of more than 500 mg/kg. The relationships of structure and activity were analyzed with 3D QSAR. The action mechanism studies revealed that the in vivo anti-tumor action of Trp-Trp-AA-OBzls was the result of DNA intercalation.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1768-3254
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pubmed:author |
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pubmed:copyrightInfo |
Copyright © 2011 Elsevier Masson SAS. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:volume |
46
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3410-9
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pubmed:meshHeading |
pubmed-meshheading:21620529-Amino Acids,
pubmed-meshheading:21620529-Animals,
pubmed-meshheading:21620529-Antineoplastic Agents,
pubmed-meshheading:21620529-Body Weight,
pubmed-meshheading:21620529-Carbolines,
pubmed-meshheading:21620529-Carcinoma, Hepatocellular,
pubmed-meshheading:21620529-Cell Line, Tumor,
pubmed-meshheading:21620529-Cell Survival,
pubmed-meshheading:21620529-Cytarabine,
pubmed-meshheading:21620529-DNA,
pubmed-meshheading:21620529-Differential Thermal Analysis,
pubmed-meshheading:21620529-Drug Screening Assays, Antitumor,
pubmed-meshheading:21620529-Esters,
pubmed-meshheading:21620529-Humans,
pubmed-meshheading:21620529-Inhibitory Concentration 50,
pubmed-meshheading:21620529-Intercalating Agents,
pubmed-meshheading:21620529-Leukemia, Myeloid,
pubmed-meshheading:21620529-Liver Neoplasms,
pubmed-meshheading:21620529-Male,
pubmed-meshheading:21620529-Melanoma,
pubmed-meshheading:21620529-Mice,
pubmed-meshheading:21620529-Mice, Inbred ICR,
pubmed-meshheading:21620529-Models, Molecular,
pubmed-meshheading:21620529-Neoplasm Transplantation,
pubmed-meshheading:21620529-Organ Size,
pubmed-meshheading:21620529-Quantitative Structure-Activity Relationship
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pubmed:year |
2011
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pubmed:articleTitle |
A class of Trp-Trp-AA-OBzl: Synthesis, in vitro anti-proliferation/in vivo anti-tumor evaluation, intercalation-mechanism investigation and 3D QSAR analysis.
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pubmed:affiliation |
College of Pharmaceutical Sciences, Capital Medical University, No. 10, Beijing 100069, PR China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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