Exploration of a binding mode of indole amide analogues as potent histone deacetylase inhibitors and 3D-QSAR analyses

Guo, Yuchen; Xiao, Jingfa; Guo, Zengjun; Chu, Frances; Cheng, Yong-Hao; Wu, Song

doi:10.1016/j.bmc.2005.05.016

Cited by 54 publications

(30 citation statements)

References 22 publications

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“…The molecular docking assay was performed as previously reported with minor modifications (Guo et al, 2005). The initial structures of the small molecular inhibitors WS010117 and AMP were constructed with the SYBYL 7.3 software, and the geometries of these compounds were subsequently optimised using the TRIPOS force field, Gasteiger-Huckel charges, and Powell methods.…”

Section: Molecular Dockingmentioning

confidence: 99%

The adenosine derivative 2′,3′,5′-tri-O-acetyl-N6-(3-hydroxylaniline) adenosine activates AMPK and regulates lipid metabolism in vitro and in vivo

et al. 2012

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Section: Molecular Dockingmentioning

confidence: 99%

The adenosine derivative 2′,3′,5′-tri-O-acetyl-N6-(3-hydroxylaniline) adenosine activates AMPK and regulates lipid metabolism in vitro and in vivo

et al. 2012

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“…Particularly, the hydroxamic acid group reaches the polar end of the pocket, where it binds the zinc residue in a bidentate fashion (through -CO and -OH groups) and the active site residues. Moreover, the hydroxamic acid function replaces the zinc-bound water molecule of the active structure with its OH group [40]. The human HDAC1 and HDAC2 are highly homologous to HDAC8, especially at the binding site.…”

Section: Hdac Inhibitorsmentioning

confidence: 99%

Histone Deacetylase Inhibitors: Molecular and Biological Activity as a Premise to Clinical Application

Santini¹,

Gozzini²,

Ferrari

2007

CDM

125

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Epigenetic modifications are reversible chromatin rearrangements that in normal cells modulate gene expression, without changing DNA sequence. Alterations of this equilibrium, mainly affecting the two interdependent mechanisms of DNA methylation and histone acetylation, are frequently involved in the genesis of cancer. The histone code, regulating gene expression, is constituted by the combination of different acetylated lysine residues of histones. In neoplastic cells, the abundance of deacetylated histones is usually associated with DNA hypermethylation and gene silencing. Several compounds, known to have in vitro antineoplastic activity, have been eventually shown to act as histone deacetylase inhibitors. Thus, HDAC inhibitors have been successfully introduced in clinical trials as antitumour agents. They are classified according to their chemical structures and are endowed with different specificity and affinity for the HDACs of classes 1, 2, 4. Among HDAC inhibitors, the most potent are the hydroxamic acid derivatives, like SAHA, which has been recently approved for therapy of cutaneous T-cell lymphomas. Other classes of HDAC inhibitors are short chain fatty acids (SCFA), benzamides, epoxyketone and non-epoxyketone containing cyclic tetrapeptides, and hybrid molecules. SCFA, although widely used (especially valproic acid) and clinically efficacious, have weak HDAC inhibition constants. Benzamides, like MS-275, and cyclic peptides, like depsipeptide, have been studied in numerous clinical trials and demonstrated low toxicity and activity in solid and haematological neoplasms. HDAC inhibitors are also potent radiation sensitizers. Their future in oncology may thus be based on their activity as single agents and on their synergy with the hypomethylating drugs and with chemo- and radiotherapeutics.

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“…75 The derived 3D-QSAR models were characterized by crossvalidated coefficient values (r 2 CV ) and conventional r 2 up to 0.601 and 0.982 for CoMFA, and 0.598 and 0.954 for CoMSIA, respectively. The structural requirements for further inhibitor design were presented by the contour maps.…”

Section: Strategies In Developing Hdaci K 591mentioning

confidence: 99%

Strategies in developing promising histone deacetylase inhibitors

Zhang

Fang

2009

Medicinal Research Reviews

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Histone deacetylases (HDACs) are a family of enzymes that have been of interest in drug discovery for more than 30 years. Inhibitors of HDACs are potential therapeutics for various diseases, such as neurodegenerative diseases, inflammation, viral infection, and especially cancer. Most HDAC inhibitors (HDACi) are designed for cancer therapy. In 2006, suberoylanilide hydroxamic acid was approved by the US Food and Drug Administration for once-daily oral treatment of advanced cutaneous T-cell lymphoma. In the meantime, there have been aggressive efforts to bring HDACi to the market for every major tumor type, either as a single therapy or in combination, and a number of compounds are currently undergoing clinical trials. Multiple strategies have been applied to the rational design of drugs targeting HDACs by taking advantage of the new developments in proteomics, chemogenomics, cheminformatics, and computational chemistry/biology. Herein, we review the current methods successfully used in developing novel HDACi.

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Exploration of a binding mode of indole amide analogues as potent histone deacetylase inhibitors and 3D-QSAR analyses

Cited by 54 publications

References 22 publications

The adenosine derivative 2′,3′,5′-tri-O-acetyl-N6-(3-hydroxylaniline) adenosine activates AMPK and regulates lipid metabolism in vitro and in vivo

The adenosine derivative 2′,3′,5′-tri-O-acetyl-N6-(3-hydroxylaniline) adenosine activates AMPK and regulates lipid metabolism in vitro and in vivo

Histone Deacetylase Inhibitors: Molecular and Biological Activity as a Premise to Clinical Application

Strategies in developing promising histone deacetylase inhibitors

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