Design, synthesis and docking studies on benzamide derivatives as histone deacetylase inhibitors

2011 ◽  
Vol 21 (16) ◽  
pp. 4924-4927 ◽  
Author(s):  
Aijun Lu ◽  
Hongpeng Luo ◽  
Minfeng Shi ◽  
Gang Wu ◽  
Yunxia Yuan ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Docking Studies ◽  
Design Synthesis ◽  
Benzamide Derivatives

Design, synthesis, docking studies and biological evaluation of novel chalcone derivatives as potential histone deacetylase inhibitors

2017 ◽  
Vol 72 ◽  
pp. 32-41 ◽  
Author(s):  
Mamdouh F.A. Mohamed ◽  
Montaser Sh.A. Shaykoon ◽  
Mostafa H. Abdelrahman ◽  
Bakheet E.M. Elsadek ◽  
Ahmed S. Aboraia ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
Chalcone Derivatives

scholarly journals Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition

2020 ◽  
Vol 16 ◽  
pp. 628-637 ◽  
Author(s):  
Sivaraman Balasubramaniam ◽  
Sajith Vijayan ◽  
Liam V Goldman ◽  
Xavier A May ◽  
Kyra Dodson ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Computational Analysis ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Design Strategies ◽  
Design Synthesis ◽  
Therapeutic Applications ◽  
Future Design ◽  
Design And Synthesis

Guided by computational analysis, herein we report the design, synthesis and evaluation of four novel diazine-based histone deacetylase inhibitors (HDACis). The targets of interest (TOI) are analogues of panobinostat, one of the most potent and versatile HDACi reported. By simply replacing the phenyl core of panobinostat with that of a diazine derivative, docking studies against HDAC2 and HDAC8 revealed that the four analogues exhibit inhibition activities comparable to that of panobinostat. Multistep syntheses afforded the visualized targets TOI1, TOI2, TOI3-rev and TOI4 whose biological evaluation confirmed the strength of HDAC8 inhibition with TOI4 displaying the greatest efficacy at varying concentrations. The results of this study lay the foundation for future design strategies toward more potent HDACis for HDAC8 isozymes and further therapeutic applications for neuroblastoma.

scholarly journals Design, Synthesis and Biological Evaluation of Novel Coumarin-Based Hydroxamate Derivatives as Histone Deacetylase (Hdac) Inhibitors with Antitumor Activities

Molecules ◽  
2019 ◽  
Vol 24 (14) ◽  
pp. 2569 ◽  
Author(s):  
Feifei Yang ◽  
Na Zhao ◽  
Jiali Song ◽  
Kongkai Zhu ◽  
Cheng-shi Jiang ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Hdac Inhibitors ◽  
A549 Cells ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Hdac Inhibition ◽  
Design Synthesis ◽  
M Phase ◽  
Ic50 Values

A series of novel coumarin-based hydroxamate derivatives were designed and synthesized as histone deacetylase inhibitors (HDACis). Selective compounds showed a potent HDAC inhibition with nM IC50 values, with the best compound (10e) being nearly 90 times more active than vorinostat (SAHA) against HDAC1. Compounds 10e and 11d also increased the levels of acetylated histone H3 and H4, which is consistent with their strong HDAC inhibition. In addition, 10e and 11d displayed a higher potency toward human A549 and Hela cancer cell lines compared with SAHA. Moreover, 10e and 11d significantly arrested A549 cells at the G2/M phase and enhanced apoptosis. Molecular docking studies revealed the possible mode of interaction of compounds 10e and 12a with HDAC1. Our findings suggest that these novel coumarin-based HDAC inhibitors provide a promising scaffold for the development of new potential cancer chemotherapies.

scholarly journals Design, Synthesis, and Blood–Brain Barrier Transport Study of Pyrilamine Derivatives as Histone Deacetylase Inhibitors

2018 ◽  
Vol 9 (9) ◽  
pp. 884-888 ◽  
Author(s):  
Seiya Hiranaka ◽  
Yuma Tega ◽  
Kei Higuchi ◽  
Toshiki Kurosawa ◽  
Yoshiharu Deguchi ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Blood Brain Barrier ◽  
Histone Deacetylase Inhibitors ◽  
Brain Barrier ◽  
Design Synthesis ◽  
Transport Study ◽  
Blood Brain

scholarly journals Novel 4-Oxoquinazoline-Based N-Hydroxypropenamides as Histone Deacetylase Inhibitors: Design, Synthesis, and Biological Evaluation

ACS Omega ◽  
2021 ◽  
Vol 6 (7) ◽  
pp. 4907-4920
Author(s):  
Duong T. Anh ◽  
Pham-The Hai ◽  
Le D. Huy ◽  
Hoang B. Ngoc ◽  
Trinh T. M. Ngoc ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
Synthesis And Biological Evaluation

scholarly journals STRUCTURAL EXPLORATION AND PHARMACOPHORIC INVESTIGATION OF PYRAZOLE BASED ANALOGS AS NOVEL HISTONE DEACETYLASE 1 INHIBITOR USING COMBINATORIAL STUDIES

2018 ◽  
Vol 10 (3) ◽  
pp. 90
Author(s):  
Avineesh Singh ◽  
Harish Rajak
Keyword(s):  
Molecular Docking ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Research Work ◽  
3D Qsar ◽  
Qsar Model ◽  
Docking Studies ◽  
Inhibition Activity ◽  
Design Strategies ◽  
Histone Deacetylase 1

Objective: Histone deacetylase inhibitors (HDACi) have four essential pharmacophores as cap group, connecting unit, a linker moiety and zinc binding group for their anticancer and histone deacetylase (HDAC) inhibition activity. On the basis of this fact, the objective of this research was to evaluate the exact role of pyrazole nucleus as connecting unit and its role in the development of newer HDACi.Methods: Ligand and structure-based computer-aided drug design strategies such as pharmacophore and atom based 3D QSAR modelling, molecular docking and energetic based pharmacophore mapping have been frequently applied to design newer analogs in a precise manner. Herein, we have applied these combinatorial approaches to develop the structure-activity correlation among novel pyrazole-based derivatives.Results: the Pharmacophore-based 3D-QSAR model was developed employing Phase module and e-pharmacophore on compound 1. This 3D-QSAR model provides fruitful information regarding favourable and unfavourable substitution on pyrazole-based analogs for HDAC1 inhibition activity. Molecular docking studies indicated that all the pyrazole derivatives bind with HDAC1 proteins and showed critical hydrophobic interaction with 5ICN and 4BKX HDAC1 proteins.Conclusion: The outcome of the present research work clearly indicated that pyrazole nucleus added an essential hydrophobic feature in cap group and could be employed to design the ligand molecules more accurately.

scholarly journals Design, synthesis and evaluation of belinostat analogs as histone deacetylase inhibitors

2019 ◽  
Vol 11 (21) ◽  
pp. 2765-2778
Author(s):  
Jie-Huan Zhang ◽  
Madhusoodanan Mottamal ◽  
Hai-Shan Jin ◽  
Shanchun Guo ◽  
Yan Gu ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Active Compound ◽  
Histone Deacetylase Inhibitors ◽  
Hdac Inhibitors ◽  
Antitumor Therapy ◽  
Design Synthesis ◽  
Inhibitory Activities ◽  
Antiproliferative Activities

Aim: Histone deacetylase (HDAC) is an attractive target for antitumor therapy. Therefore, the development of novel HDAC inhibitors is warranted. Materials & methods: A series of HDAC inhibitors based on N-hydroxycinnamamide fragment was designed as the clinically used belinostat analog using amide as the connecting unit. All target compounds were evaluated for their in vitro HDAC inhibitory activities and some selected compounds were tested for their antiproliferative activities. Conclusion: Among them, compound 7e showed an IC50 value of 11.5 nM in inhibiting the HDAC in a pan-HDAC assay, being the most active compound of the series.

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