Non-Peptide Macrocyclic Histone Deacetylase Inhibitors
العنوان: | Non-Peptide Macrocyclic Histone Deacetylase Inhibitors |
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المؤلفون: | Adegboyega K. Oyelere, Po C. Chen, Yunzhe Zhang, William Guerrant, Sandra C. Mwakwari, Yuhong Fan, Rebecca Hood |
المصدر: | Journal of Medicinal Chemistry. 52:456-468 |
بيانات النشر: | American Chemical Society (ACS), 2008. |
سنة النشر: | 2008 |
مصطلحات موضوعية: | Depsipeptide, chemistry.chemical_classification, Macrocyclic Compounds, Magnetic Resonance Spectroscopy, Stereochemistry, Peptide, Spectrometry, Mass, Fast Atom Bombardment, Small molecule, Non peptide, Article, Cell Line, Histone Deacetylase Inhibitors, Structure-Activity Relationship, Transformed cell, Biochemistry, chemistry, Cell culture, Drug Discovery, Humans, Molecular Medicine, Structure–activity relationship, Histone deacetylase, Enzyme Inhibitors |
الوصف: | Inhibition of histone deacetylase inhibitors (HDACi) hold great promise in cancer therapy because of their demonstrated ability to arrest proliferation of nearly all transformed cell types. Of the several structurally distinct small molecule HDACi reported, macrocyclic depsipeptides have the most complex recognition cap-group moieties and present an excellent opportunity for the modulation of the biological activities of HDACi. Unfortunately, the structure-activity relationship (SAR) studies for this class of compounds have been impaired largely because most macrocyclic HDACi known to date comprise complex peptide macrocycles. In addition to retaining the pharmacologically disadvantaged peptidyl backbone, they offer only limited opportunity for side chain modifications. Here, we report the discovery of a new class of macrocyclic HDACi based on the macrolide antibiotics skeletons. SAR studies revealed that these compounds displayed both linker-length and macrolide-type dependent HDAC inhibition activities with IC(50) in the low nanomolar range. In addition, these non-peptide macrocyclic HDACi are more selective against HDACs 1 and 2 relative to HDAC 8, another class I HDAC isoform, and hence have subclass HDAC isoform selectivity. |
تدمد: | 1520-4804 0022-2623 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::77b90bd424581c20e8499c58e58cd528 https://doi.org/10.1021/jm801128g |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....77b90bd424581c20e8499c58e58cd528 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 15204804 00222623 |
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