Design, synthesis and biological evaluation of novel histone deacetylase (HDAC) inhibitors derived from
            <i>β</i>
            -elemene scaffold

Gao, Yuan; Duan, Jilong; Dang, Xiawen; Yuan, Yinghui; Wang, Yu; He, Xingrui; Bai, Renren; Ye, Xiang‐Yang; Xie, Tian

doi:10.1080/14756366.2023.2195991

Cited by 8 publications

(2 citation statements)

References 46 publications

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“…More recently, Gao and co-workers developed and synthesized novel HDAC inhibitors derived from the β-elemene scaffold [234]. β-elemene is specifically a sesquiterpene used in the treatment of lung cancer, pancreatic cancer, gastric cancer, breast cancer, bladder cancer, and malignant brain glioma [235][236][237][238][239][240].…”

Section: Molecular Modelingmentioning

confidence: 99%

The Histone Deacetylase Family: Structural Features and Application of Combined Computational Methods

Curcio,

Rocca,

Alcaro

et al. 2024

Pharmaceuticals

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Histone deacetylases (HDACs) are crucial in gene transcription, removing acetyl groups from histones. They also influence the deacetylation of non-histone proteins, contributing to the regulation of various biological processes. Thus, HDACs play pivotal roles in various diseases, including cancer, neurodegenerative disorders, and inflammatory conditions, highlighting their potential as therapeutic targets. This paper reviews the structure and function of the four classes of human HDACs. While four HDAC inhibitors are currently available for treating hematological malignancies, numerous others are undergoing clinical trials. However, their non-selective toxicity necessitates ongoing research into safer and more efficient class-selective or isoform-selective inhibitors. Computational methods have aided the discovery of HDAC inhibitors with the desired potency and/or selectivity. These methods include ligand-based approaches, such as scaffold hopping, pharmacophore modeling, three-dimensional quantitative structure–activity relationships, and structure-based virtual screening (molecular docking). Moreover, recent developments in the field of molecular dynamics simulations, combined with Poisson–Boltzmann/molecular mechanics generalized Born surface area techniques, have improved the prediction of ligand binding affinity. In this review, we delve into the ways in which these methods have contributed to designing and identifying HDAC inhibitors.

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Section: Molecular Modelingmentioning

confidence: 99%

The Histone Deacetylase Family: Structural Features and Application of Combined Computational Methods

Curcio,

Rocca,

Alcaro

et al. 2024

Pharmaceuticals

View full text Add to dashboard Cite

show abstract

“…These results further affirmed that dual-targeting PARP1 and other proteins of interest could benefit in treating diseases. Our laboratory has been working on several HDACs-related projects, , as well as dual inhibitors involving HDACs . Literature search revealed that no PARP7/HDACs dual inhibitor has been reported to date.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Structure–Activity Relationship of Novel Pyridazinone-Based PARP7/HDACs Dual Inhibitors for Elucidating the Relationship between Antitumor Immunity and HDACs Inhibition

Duan,

Wang,

Yuan

et al. 2024

J. Med. Chem.

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Histone deacetylases (HDACs) inhibitors such as vorinostat (SAHA) has been used to treat hematologic malignancies (rather than solid tumors) and have been found to suppress the JAK/STAT, a critical signal pathway for antitumor immunity, while PARP7 inhibitor RBN-2397 could activate the type I interferons (IFN-I) pathway, facilitating downstream effects such as STAT1 phosphorylation and immune activation. To elucidate whether simultaneous inhibition of these two targets could interfere with these two signal pathways, a series of pyridazinone-based PARP7/HDACs dual inhibitors have been designed, synthesized, and evaluated 7 inhibitor RBN-2397 could activate the type I interferons (IFN-I) pathway, facilitating downstream effects such as STAT1 phosphorylation and immune activation. To elucidate whether simultaneous inhibition of these two targets could interfere with these two signal pathways, a series of pyridazinone-based PARP7/HDACs dual inhibitors have been designed, synthesized, and evaluated in vitro and in vivo experiments. Compound 9l was identified as a potent and balanced dual inhibitor for the first time, exhibiting excellent antitumor capabilities both in vitro and in vivo. This suggests that 9l can be used as a valuable tool molecule for investigating the relationship between anticancer immunity and HDAC inhibition.

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Hydroxamic acid hybrids: Histone deacetylase inhibitors with anticancer therapeutic potency

Pan,

Hou,

Zhou

et al. 2023

European Journal of Medicinal Chemistry

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Design, synthesis and biological evaluation of novel histone deacetylase (HDAC) inhibitors derived from β -elemene scaffold

Cited by 8 publications

References 46 publications

The Histone Deacetylase Family: Structural Features and Application of Combined Computational Methods

The Histone Deacetylase Family: Structural Features and Application of Combined Computational Methods

Design, Synthesis, and Structure–Activity Relationship of Novel Pyridazinone-Based PARP7/HDACs Dual Inhibitors for Elucidating the Relationship between Antitumor Immunity and HDACs Inhibition

Hydroxamic acid hybrids: Histone deacetylase inhibitors with anticancer therapeutic potency

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