Design, synthesis and biological evaluation of coumarin-based N-hydroxycinnamamide derivatives as novel histone deacetylase inhibitors with anticancer activities

Ding, Jiaoli; Liu, Jing; Zhang, Zhipeng; Guo, Jie; Cheng, Maojun; Wan, Yang; Wang, Rikang; Yuan, Fang; Guan, Zhiwei; Jin, Yi; Xie, Sai‐Sai

doi:10.1016/j.bioorg.2020.104023

Cited by 22 publications

(14 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Even that, only a few recent studies include a computational characterization of coumarin based compounds as a HDAC Inhibitor. Regarding with this, Zhang and coworkers in recent research indicate the effectiveness of having a coumarin moiety as the main structure for its modification and application as anticancer agents, in combination with an hydroxamic acid functionalization to potentialize the activity ( Figure 2) [24][25][26]. This kind of information is a strong background to embrace the hypothesis of the present work.…”

Section: Introductionmentioning

confidence: 54%

Design of Fluorescent Coumarin-Hydroxamic Acid Derivatives as Inhibitors of HDACs: Synthesis, Anti-Proliferative Evaluation and Docking Studies

et al. 2020

View full text Add to dashboard Cite

Coumarin-hydroxamic acid derivatives 7a–k were herein designed with a dual purpose: as antiproliferative agents and fluorescent probes. The compounds were synthesized in moderate yields (30–87%) through a simple methodology, biological evaluation was carried out on prostate (PC3) and breast cancer (BT-474 and MDA-MB-231) cell lines to determine the effects on cell proliferation and gene expression. For compounds 7c, 7e, 7f, 7i and 7j the inhibition of cancer cell proliferation was similar to that found with the reference compound at a comparable concentration (10 μM), in addition, their molecular docking studies performed on histone deacetylases 1, 6 and 8 showed strong binding to the respective active sites. In most cases, antiproliferative activity was accompanied by greater levels of cyclin-dependent kinase inhibitor p21, downregulation of the p53 tumor suppressor gene, and regulation of cyclin D1 gene expression. We conclude that compounds 7c, 7e, 7f, 7i and 7j may be considered as potential anticancer agents, considering their antiproliferative properties, their effect on the regulation of the genes, as well as their capacity to dock to the active sites. The fluorescent properties of compound 7j and 7k suggest that they can provide further insight into the mechanism of action.

show abstract

Section: Introductionmentioning

confidence: 54%

Design of Fluorescent Coumarin-Hydroxamic Acid Derivatives as Inhibitors of HDACs: Synthesis, Anti-Proliferative Evaluation and Docking Studies

et al. 2020

View full text Add to dashboard Cite

show abstract

“…As well as, compound 11f could decreased the colony formation and raised the acetylation of histone H3 in a dose-dependent manner, and it could also induce apoptosis and cell cycle arrest at G2/M phase in HeLa cells. Overall, all these findings supposed that compound 11f was a novel promising moiety as HDAC inhibitor with anticancer activity [12] . A novel series of coumarin-based hydroxamate derivatives as as HDACs inhibitors (Fig.…”

Section: Fig 1 Structure Of Coumarinmentioning

confidence: 83%

“…65, No. 7 (2022) the active site of HDAC through interacting with the residues at the entrance of the protein [12].…”

Section: Introductionmentioning

confidence: 99%

Coumarin based-histone deactylace HADC inhibitors

jabbar

mohammed

2021

Egypt. J. Chem.

View full text Add to dashboard Cite

Coumarins have been recognized as anticancer competitors. HDACis are one of the interesting issues in the field of antitumor research. In order to achieve an increased anticancer efficacy, a series of hybrid compounds bearing coumarin scaffolds have been designed and synthesized as novel HDACis, In this review we present a series of novel HDAC inhibitors comprising coumarin as a core e of cap group of HDAC inhibitors that have been designed, synthesized and assessed for their enzyme inhibitory activity as well as antiproliferative activity. Most of them exhibited potent HDAC inhibitory activity and significant cytotoxicity

show abstract

“…HDACi treatment can promote cell apoptosis by the extrinsic/intrinsic pathway and by improving the sensitivity of tumour cells ( 162 ). In addition, some HDACis have been assessed in preclinical cancer models.…”

Section: Possible Mechanisms Of Hdacs In Cancer Developmentmentioning

confidence: 99%

Characterization of Histone Deacetylase Mechanisms in Cancer Development

Hai

Shu

et al. 2021

Front. Oncol.

View full text Add to dashboard Cite

Over decades of studies, accumulating evidence has suggested that epigenetic dysregulation is a hallmark of tumours. Post-translational modifications of histones are involved in tumour pathogenesis and development mainly by influencing a broad range of physiological processes. Histone deacetylases (HDACs) and histone acetyltransferases (HATs) are pivotal epigenetic modulators that regulate dynamic processes in the acetylation of histones at lysine residues, thereby influencing transcription of oncogenes and tumour suppressor genes. Moreover, HDACs mediate the deacetylation process of many nonhistone proteins and thus orchestrate a host of pathological processes, such as tumour pathogenesis. In this review, we elucidate the functions of HDACs in cancer.

show abstract

Design, synthesis and biological evaluation of coumarin-based N-hydroxycinnamamide derivatives as novel histone deacetylase inhibitors with anticancer activities

Cited by 22 publications

References 42 publications

Design of Fluorescent Coumarin-Hydroxamic Acid Derivatives as Inhibitors of HDACs: Synthesis, Anti-Proliferative Evaluation and Docking Studies

Design of Fluorescent Coumarin-Hydroxamic Acid Derivatives as Inhibitors of HDACs: Synthesis, Anti-Proliferative Evaluation and Docking Studies

Coumarin based-histone deactylace HADC inhibitors

Characterization of Histone Deacetylase Mechanisms in Cancer Development

Contact Info

Product

Resources

About