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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 |
2010-4-15
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pubmed:abstractText |
A series of SAHA cap derivatives was designed and prepared in good-to-excellent yields that varied from 49% to 95%. These derivatives were evaluated for their antiproliferative activity in several human cancer cell lines. Antiproliferative activity was observed for concentrations varying from 0.12 to >100 microM, and a molecular modeling approach of selected SAHA derivatives, based on available structural information of human HDAC8 in complex with SAHA, was performed. Strikingly, two compounds displayed up to 10-fold improved antileukemic activity with respect to SAHA; however, these compounds displayed antiproliferative activity similar to SAHA when assayed against solid tumor-derived cell lines. A 10-fold improvement in the leukemic vs peripheral blood mononuclear cell therapeutic ratio, with no evident in vivo toxicity toward blood cells, was also observed. The herein-described compounds and method of synthesis will provide invaluable tools to investigate the molecular mechanism responsible for the reported selectively improved antileukemic activity.
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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 |
Apr
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pubmed:issn |
1520-4804
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
22
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pubmed:volume |
53
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3038-47
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pubmed:meshHeading |
pubmed-meshheading:20218673-Animals,
pubmed-meshheading:20218673-Antineoplastic Agents,
pubmed-meshheading:20218673-Blood Cell Count,
pubmed-meshheading:20218673-Cell Line, Tumor,
pubmed-meshheading:20218673-Drug Screening Assays, Antitumor,
pubmed-meshheading:20218673-Histone Deacetylase Inhibitors,
pubmed-meshheading:20218673-Histone Deacetylases,
pubmed-meshheading:20218673-Humans,
pubmed-meshheading:20218673-Hydroxamic Acids,
pubmed-meshheading:20218673-Leukemia,
pubmed-meshheading:20218673-Mice,
pubmed-meshheading:20218673-Models, Molecular,
pubmed-meshheading:20218673-Repressor Proteins,
pubmed-meshheading:20218673-Structure-Activity Relationship,
pubmed-meshheading:20218673-Toxicity Tests, Chronic
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pubmed:year |
2010
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pubmed:articleTitle |
Modified cap group suberoylanilide hydroxamic acid histone deacetylase inhibitor derivatives reveal improved selective antileukemic activity.
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pubmed:affiliation |
Unite 891 INSERM, Centre de Recherche en Cancerologie de Marseille, 27 Bd Lei Roure, 13009 Marseille 09, France.
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pubmed:publicationType |
Journal Article
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