https://scholars.lib.ntu.edu.tw/handle/123456789/560403
標題: | Synthesis and evaluation of aliphatic-chain hydroxamates capped with osthole derivatives as histone deacetylase inhibitors | 作者: | Huang W.-J. CHING-CHOW CHEN Chao S.-W. Yu C.-C. Yang C.-Y. JIH-HWA GUH Lin Y.-C. Kuo C.-I. Yang P. Chang C.-I. |
公開日期: | 2011 | 卷: | 46 | 期: | 9 | 起(迄)頁: | 4042-4049 | 來源出版物: | European Journal of Medicinal Chemistry | 摘要: | Our previous studies have demonstrated that osthole, a Chinese herbal compound, could be incorporated into the hydroxycinnamide scaffold of LBH-589, a potent HDAC inhibitor, as an effective hydrophobic cap; the resulting compounds showed significant potency against several HDAC isoforms. Here, we presented a series of osthole derivatives fused with the aliphatic-hydroxamate core of suberoylanilide hydroxamic acid (SAHA), a clinically-approved HDAC inhibitor. Several compounds showed potent activity against nuclear HDACs. Further assays against individual HDAC isoforms revealed that some compounds showed not only SAHA-like activity towards HDAC1, -4 and -6, they inhibited HDAC8 by log difference than SAHA and thus exhibited a broader HDAC inhibition spectrum. Among them, compound 6g showed potent antiproliferative effect on several human cancer cell lines. ? 2011 Elsevier Masson SAS. All rights reserved. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/560403 | ISSN: | 2235234 | DOI: | 10.1016/j.ejmech.2011.06.002 | SDG/關鍵字: | antineoplastic agent; histone deacetylase 8; histone deacetylase inhibitor; n hydroxy 5 (3 hydroxy 4 (2 hydroxycarbamoylethyl) 2 isopentyl phenoxy) pentanamide; n hydroxy 5 (3,4 dihydro 8 isopentyl 2 oxo 2h chromen 7 yloxy)pentanamide; n hydroxy 5 (8 isopentyl 2 oxo 2h chromen 7 yloxy)pentanamide; n hydroxy 6 (3 hydroxy 4 (2 hydroxycarbamoylethyl) 2 isopentyl phenoxy) hexanamide; n hydroxy 6 (3,4 dihydro 8 isopentyl 2 oxo 2h chromen 7 yloxy)hexanamide; n hydroxy 6 (8 isopentyl 2 oxo 2h chromen 7 yloxy)hexanamide; n hydroxy 7 (3 hydroxy 4 (2 hydroxycarbamoylethyl) 2 isopentyl-phenoxy) heptanamide; n hydroxy 7 (3,4 dihydro 8 isopentyl 2 oxo 2h chromen 7 yloxy)heptanamide; n hydroxy 7 (8 isopentyl 2 oxo 2h chromen 7 yloxy)heptanamide; n hydroxy 8 (3 hydroxy 4 (2 hydroxycarbamoylethyl) 2 isopentyl phenoxy) octanamide; n hydroxy 8 (3,4 dihydro 8 isopentyl 2 oxo 2h chromen 7 yloxy)octanoate; n hydroxy 8 (8 isopentyl 2 oxo 2h chromen 7 yloxy)octanamide; osthole; unclassified drug; vorinostat; antineoplastic activity; article; cancer cell culture; drug activity; drug screening; drug synthesis; human; human cell; inhibition kinetics; neoplasm; Blotting, Western; Histone Deacetylase Inhibitors; Histone Deacetylases; Humans; Hydroxamic Acids; Protein Conformation; Spectrometry, Mass, Electrospray Ionization |
顯示於: | 藥理學科所 |
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