scholarly journals Synthesis of hybrid anticancer agents based on kinase and histone deacetylase inhibitors

MedChemComm ◽  
2014 ◽  
Vol 5 (12) ◽  
pp. 1829-1833 ◽  
Author(s):  
Hiren Patel ◽  
Irina Chuckowree ◽  
Peter Coxhead ◽  
Matthew Guille ◽  
Minghua Wang ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Anticancer Agents ◽  
Histone Deacetylase Inhibitors ◽  
Kinase Inhibitor

A HDAC, kinase inhibitor hybrid, (Z)-N1-(3-((1H-pyrrol-2-yl)methylene)-2-oxoindolin-5-yl)-N8-hydroxyoctanediamide, 6, showed impressive anticancer action in a number of biochemical and cell-based assays.

Histone Deacetylase Inhibitors: A New Wave of Molecular Targeted Anticancer Agents

2007 ◽  
Vol 2 (2) ◽  
pp. 119-134 ◽  
Author(s):  
Alfredo Budillon ◽  
Elena Di Gennaro ◽  
Francesca Bruzzese ◽  
Monia Rocco ◽  
Giuseppe Manzo ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Anticancer Agents ◽  
Histone Deacetylase Inhibitors ◽  
New Wave

New histone deacetylase inhibitors and anticancer agents from Curcuma longa

2019 ◽  
Vol 28 (10) ◽  
pp. 1773-1782 ◽  
Author(s):  
Pakit Kumboonma ◽  
Thanaset Senawong ◽  
Somprasong Saenglee ◽  
Gulsiri Senawong ◽  
La-or Somsakeesit ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Anticancer Agents ◽  
Histone Deacetylase Inhibitors ◽  
Curcuma Longa

Recent Progress in Histone Deacetylase Inhibitors as Anticancer Agents

2020 ◽  
Vol 27 (15) ◽  
pp. 2449-2493 ◽  
Author(s):  
Loredana Cappellacci ◽  
Diego R. Perinelli ◽  
Filippo Maggi ◽  
Mario Grifantini ◽  
Riccardo Petrelli
Keyword(s):  
Clinical Trials ◽  
Histone Deacetylase ◽  
Anticancer Agents ◽  
Histone Deacetylase Inhibitors ◽  
Cyclic Peptide ◽  
Hdac Inhibitors ◽  
Cancer Therapeutics ◽  
Rational Drug Design ◽  
Modeling Tools ◽  
Anti Cancer

Histone Deacetylase (HDAC) inhibitors are a relatively new class of anti-cancer agents that play important roles in epigenetic or non-epigenetic regulation, inducing death, apoptosis, and cell cycle arrest in cancer cells. Recently, their use has been clinically validated in cancer patients resulting in the approval by the FDA of four HDAC inhibitors, vorinostat, romidepsin, belinostat and panobinostat, used for the treatment of cutaneous/peripheral T-cell lymphoma and multiple myeloma. Many more HDAC inhibitors are at different stages of clinical development for the treatment of hematological malignancies as well as solid tumors. Also, clinical trials of several HDAC inhibitors for use as anti-cancer drugs (alone or in combination with other anti-cancer therapeutics) are ongoing. In the intensifying efforts to discover new, hopefully, more therapeutically efficacious HDAC inhibitors, molecular modelingbased rational drug design has played an important role. In this review, we summarize four major structural classes of HDAC inhibitors (hydroxamic acid derivatives, aminobenzamide, cyclic peptide and short-chain fatty acids) that are in clinical trials and different computer modeling tools available for their structural modifications as a guide to discover additional HDAC inhibitors with greater therapeutic utility.

Histone Deacetylase Inhibitors and Papillary Thyroid Cancer

2020 ◽  
Vol 26 ◽  
Author(s):  
Eleftherios Spartalis ◽  
Konstantinos Kotrotsios ◽  
Dimosthenis Chrysikos ◽  
Michael Spartalis ◽  
Stavroula A. Paschou ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Histone Deacetylase ◽  
Papillary Thyroid Cancer ◽  
Anticancer Agents ◽  
Histone Deacetylase Inhibitors ◽  
Trichostatin A ◽  
Potential Effect ◽  
Papillary Thyroid ◽  
Major Response ◽  
Anti Cancer

Background/Aim: Papillary Thyroid Cancer (PTC) is the most common type of endocrine malignancy. Although PTC has an excellent prognosis, recurrent or metastatic disease could affect patients survival. Recent studies show that Histone Deacetylase Inhibitors (HDACIs) might be promising anticancer agents against PTC. The aim of this review is to evaluate the role of HDACIs as an additional modality in PTC treatment and to depict the latest trends of current research on this field. Materials and Methods: This literature review was performed using the MEDLINE database. The search strategy included terms: “thyroid cancer”, “papillary”, “HDAC”, “histone”, and “deacetylase”. Results: Agents, such as Suberoyl Anilide Hydroxamic Acid, Trichostatin A, Valproic Acid, Sodium butyrate, Panobinostat, Belinostat, Romidepsin, CUDC907 and N-Hydroxy-7-(2-naphthylthio)-Hepanomide have shown promising anti-cancer effects on PTC cell lines but fail to trigger major response in clinical trials. Conclusion: HDACIs have no significant effect as monotherapy against PTC but further research needs to be conducted in order to investigate their potential effect when used as an additional modality.

Design, Synthesis and Evaluation of Novel 3/4-((Substituted benzamidophenoxy) methyl)-N-hydroxybenzamides/propenamides as Histone Deacetylase Inhibitors and Antitumor Agents

2019 ◽  
Vol 19 (4) ◽  
pp. 546-556
Author(s):  
Duong T. Anh ◽  
Nguyen T. Thuan ◽  
Pham-The Hai ◽  
Le-Thi-Thu Huong ◽  
Nguyen T.K. Yen ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Histone Deacetylase Inhibitors ◽  
Antitumor Agents ◽  
Human Cancer ◽  
Hdac Inhibitors ◽  
Cancer Cell Lines ◽  
Inhibitory Potency

Background: Histone Deacetylase (HDAC) inhibitors represent an extensive class of targeted anticancer agents. Among the most explored structure moieties, hydroxybenzamides and hydroxypropenamides have been demonstrated to have potential HDAC inhibitory effects. Several compounds of these structural classes have been approved for clinical uses to treat different types of cancer, such as givinostat (ITF2357) and belinostat (PXD-101). Aims: This study aims at developing novel HDAC inhibitors bearing N-hydroxybenzamides and Nhydroxypropenamides scaffolds with potential cytotoxicity against different cancer cell lines. Methods: Two new series of N-hydroxybenzamides and N-hydroxypropenamides analogues (4a-j, 6a-j) designed based on the structural features of nexturastat A, AR-42, and PXD-101, were synthesized and evaluated for HDAC inhibitory potency as well as cytotoxicity against three human cancer cell lines (SW620 (colorectal adenocarcinoma), PC3 (prostate adenocarcinoma), and NCI-H23 (adenocarcinoma, non-small cell lung cancer). Molecular simulations were finally carried out to gain more insight into the structure-activity relationships. Results: It was found that the N-hydroxypropenamides (6a-e) displayed very good HDAC inhibitory potency and cytotoxicity. Various compounds, e.g. 6a-e, especially compound 6e, were up to 5-fold more potent than suberanilohydroxamic acid (SAHA) in terms of cytotoxicity. These compounds also comparably inhibited HDACs with IC50 values in the sub-micromolar range. Docking experiments showed that these compounds bound to HDAC2 at the enzyme active binding site with the same binding mode of SAHA, but with higher binding affinities. Conclusions: The two series of N-hydroxybenzamides and N-hydroxypropenamides designed and synthesized were potential HDAC inhibitors and antitumor agents. Further development of these compounds should be warranted.

scholarly journals Histone Deacetylase Inhibitors Increase p27Kip1by Affecting Its Ubiquitin-Dependent Degradation through Skp2 Downregulation

2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Adriana Borriello ◽  
Silvio Naviglio ◽  
Debora Bencivenga ◽  
Ilaria Caldarelli ◽  
Annunziata Tramontano ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Posttranslational Modifications ◽  
Histone Deacetylase Inhibitors ◽  
Kinase Inhibitor ◽  
Protein Levels ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Skp2 Protein ◽  
Pharmacologically Active ◽  
Pharmacologically Active Compounds

Histone deacetylase inhibitors (HDACIs) represent an intriguing class of pharmacologically active compounds. Currently, some HDACIs are FDA approved for cancer therapy and many others are in clinical trials, showing important clinical activities at well tolerated doses. HDACIs also interfere with the aging process and are involved in the control of inflammation and oxidative stress.In vitro, HDACIs induce different cellular responses including growth arrest, differentiation, and apoptosis. Here, we evaluated the effects of HDACIs on p27Kip1, a key cyclin-dependent kinase inhibitor (CKI). We observed that HDACI-dependent antiproliferative activity is associated with p27Kip1accumulation due to a reduced protein degradation. p27Kip1removal requires a preliminary ubiquitination step due to the Skp2-SCF E3 ligase complex. We demonstrated that HDACIs increase p27Kip1stability through downregulation of Skp2 protein levels. Skp2 decline is only partially due to a reduced Skp2 gene expression. Conversely, the protein decrease is more profound and enduring compared to the changes of Skp2 transcript. This argues for HDACIs effects on Skp2 protein posttranslational modifications and/or on its removal. In summary, we demonstrate that HDACIs increase p27Kip1by hampering its nuclear ubiquitination/degradation. The findings might be of relevance in the phenotypic effects of these compounds, including their anticancer and aging-modulating activities.

Largazole Analogues as Histone Deacetylase Inhibitors and Anticancer Agents: An Overview of Structure-Activity Relationships

ChemMedChem ◽  
2017 ◽  
Vol 12 (23) ◽  
pp. 1917-1926 ◽  
Author(s):  
Giulio Poli ◽  
Romano Di Fabio ◽  
Luca Ferrante ◽  
Vincenzo Summa ◽  
Maurizio Botta
Keyword(s):  
Histone Deacetylase ◽  
Anticancer Agents ◽  
Histone Deacetylase Inhibitors ◽  
Structure Activity Relationships ◽  
Structure Activity
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