Development of Tetrahydroisoquinoline-Based Hydroxamic Acid Derivatives: Potent Histone Deacetylase Inhibitors with Marked in Vitro and in Vivo Antitumor Activities

2011 ◽  
Vol 54 (8) ◽  
pp. 2823-2838 ◽  
Author(s):  
Yingjie Zhang ◽  
Jinhong Feng ◽  
Yuping Jia ◽  
Xuejian Wang ◽  
Lei Zhang ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Hydroxamic Acid ◽  
Histone Deacetylase Inhibitors ◽  
Antitumor Activities ◽  
Hydroxamic Acid Derivatives

scholarly journals Histone Deacetylase Inhibitors with Enhanced Enzymatic Inhibition Effects and Potent in vitro and in vivo Antitumor Activities

ChemMedChem ◽  
2013 ◽  
Vol 9 (3) ◽  
pp. 638-648 ◽  
Author(s):  
Lei Zhang ◽  
Yingjie Zhang ◽  
C. James Chou ◽  
Elizabeth S. Inks ◽  
Xuejian Wang ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Antitumor Activities ◽  
Enzymatic Inhibition

scholarly journals In Vitro Assessment of the Genotoxic Hazard of Novel Hydroxamic Acid- and Benzamide-Type Histone Deacetylase Inhibitors (HDACi)

2020 ◽  
Vol 21 (13) ◽  
pp. 4747
Author(s):  
Annabelle Friedrich ◽  
Ann-Sophie Assmann ◽  
Lena Schumacher ◽  
Jana v. Stuijvenberg ◽  
Matthias U. Kassack ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Hydroxamic Acid ◽  
Histone Deacetylase Inhibitors ◽  
Excision Repair ◽  
Strand Break ◽  
In Vivo Studies ◽  
Therapeutic Window ◽  
V79 Cells

Histone deacetylase inhibitors (HDACi) are already approved for the therapy of leukemias. Since they are also emerging candidate compounds for the treatment of non-malignant diseases, HDACi with a wide therapeutic window and low hazard potential are desirable. Here, we investigated a panel of 12 novel hydroxamic acid- and benzamide-type HDACi employing non-malignant V79 hamster cells as toxicology guideline-conform in vitro model. HDACi causing a ≥10-fold preferential cytotoxicity in malignant neuroblastoma over non-malignant V79 cells were selected for further genotoxic hazard analysis, including vorinostat and entinostat for control. All HDACi selected, (i.e., KSK64, TOK77, DDK137 and MPK77) were clastogenic and evoked DNA strand breaks in non-malignant V79 cells as demonstrated by micronucleus and comet assays, histone H2AX foci formation analyses (γH2AX), DNA damage response (DDR) assays as well as employing DNA double-strand break (DSB) repair-defective VC8 hamster cells. Genetic instability induced by hydroxamic acid-type HDACi seems to be independent of bulky DNA adduct formation as concluded from the analysis of nucleotide excision repair (NER) deficient mutants. Summarizing, KSK64 revealed the highest genotoxic hazard and DDR stimulating potential, while TOK77 and MPK77 showed the lowest DNA damaging capacity. Therefore, these compounds are suggested as the most promising novel candidate HDACi for subsequent pre-clinical in vivo studies.

Discovery of Novel Class I Histone Deacetylase Inhibitors with Promising in Vitro and in Vivo Antitumor Activities

2015 ◽  
Vol 58 (19) ◽  
pp. 7672-7680 ◽  
Author(s):  
Yiwu Yao ◽  
Zhengchao Tu ◽  
Chenzhong Liao ◽  
Zhen Wang ◽  
Shang Li ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Class I ◽  
Antitumor Activities

Histone Deacetylase Inhibitors: Assays to Assess Effectiveness In Vitro and In Vivo

2003 ◽  
pp. 199-205 ◽  
Author(s):  
Victoria M Richon ◽  
Xianbo Zhou ◽  
J.Paul Secrist ◽  
Carlos Cordon-Cardo ◽  
W.Kevin Kelly ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors
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