Article
Biochemistry & Molecular Biology
Jakub Ptacek, Ivan Snajdr, Jiri Schimer, Zsofia Kutil, Jana Mikesova, Petra Baranova, Barbora Havlinova, Werner Tueckmantel, Pavel Majer, Alan Kozikowski, Cyril Barinka
Summary: This article compares hydroxamate-based HDAC6-selective inhibitors commonly used in the treatment of neurological and psychiatric disorders with a novel HDAC6 inhibitor containing the difluoromethyl-1,3,4-oxadiazole function (compound 7). In vitro screening revealed HDAC10 as a primary off-target for hydroxamate-based HDAC6 inhibitors, while compound 7 showed exquisite selectivity over all other HDAC isoforms. Cell-based assays showed lower potency for all compounds when using tubulin acetylation as a surrogate readout. Additionally, the limited selectivity of some HDAC6 inhibitors was shown to be linked to cytotoxicity in RPMI-8226 cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Sadiya Khwaja, Kapil Kumar, Ranjana Das, Arvind Singh Negi
Summary: The dynamic equilibrium of tubulin-microtubule is crucial for cell survival, making it an important target for cancer drug development. Microtubules play essential roles in mitosis and cell multiplication, while MAPs interact with microtubules to affect their stability. Post-translational modifications of lysine-40 and HDAC inhibitors have significant roles in gene expression and anticancer properties, respectively.
BIOORGANIC CHEMISTRY
(2021)
Review
Pharmacology & Pharmacy
Hae Jin Kee, Inkyeom Kim, Myung Ho Jeong
Summary: This article provides an overview of the pathogenesis of hypertension, current anti-hypertensive drugs, and the need for novel drugs. It focuses on the role and regulatory mechanisms of HDACs in hypertension and discusses the progress in developing HDAC inhibitors as potential therapeutic targets.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Chen Chen, Xue Li, Huajun Zhao, Meng Liu, Jintong Du, Jian Zhang, Xinying Yang, Xuben Hou, Hao Fang
Summary: The combined use of a DNA minor groove binder and a histone deacetylase (HDAC) inhibitor has shown a synergistic antiproliferation effect. A new series of benzimidazole-hydroxamate hybrids were designed and synthesized to target both DNA minor groove and HDAC. The most active compounds 9k and 9l not only exhibited improved HDAC inhibitory activities but also showed potent antiproliferation activities against tumor cells. Importantly, these compounds demonstrated good in vivo antitumor efficacies and reshaped the tumor immune microenvironment by promoting antigen presentation, activating T cells, and polarizing tumor-infiltrating macrophages with antitumor activity.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Chemistry, Medicinal
Sharba Tasneem, Mohammad Mumtaz Alam, Mohammad Amir, Mymoona Akhter, Suhel Parvez, Garima Verma, Lalit Mohan Nainwal, Ashif Equbal, Tarique Anwer, Mohammad Shaquiquzzaman
Summary: The regulation of genes through post-translational modification of proteins, known as "epigenetic" regulation, has been extensively studied for disease therapies, especially cancer chemotherapeutics. Histone deacetylases (HDACs) are important targets in epigenetic regulation and play a crucial role in balancing acetylation/deacetylation of lysine amino acids on histone/nonhistone proteins. HDAC inhibitors (HDACIs) are biologically active compounds that have become essential for cancer treatment due to their ability to induce cell cycle arrest, differentiation, and apoptosis in tumor cells.
MINI-REVIEWS IN MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Ping Shi, Lan B. Hoang-Minh, Jia Tian, Alice Cheng, Reemsha Basrai, Neil Kalaria, Joseph J. Lebowitz, Habibeh Khoshbouei, Loic P. Deleyrolle, Matthew R. Sarkisian
Summary: HDAC6 plays a critical role in promoting the proliferation of glioma cells through primary cilia, and inhibiting HDAC6 activity leads to reduced tumor cell proliferative capacity and increased cell differentiation, dependent on the presence of cilia in the cells.
Article
Cell Biology
Kyle N. Hearn, Trent D. Ashton, Rameshwor Acharya, Zikai Feng, Nuri Gueven, Frederick M. Pfeffer
Summary: The methodology of accessing fluorescent 3-amido-1,8-naphthalimides using direct Buchwald-Hartwig amidation was described and successfully applied to synthesize a series of new compounds with high activity performance. The new compounds showed higher potency than scriptaid at multiple HDAC isoforms and were more active in a tubulin deacetylation assay compared to the established HDAC6 selective inhibitor Tubastatin, making them suitable for cellular imaging studies and theranostic applications.
Article
Plant Sciences
Chun Lei, Ya-Nan Li, Jia-Nan Li, Yu-Bo Zhou, Ming-Jun Cui, Kai-Cong Fu, Jia Li, Ai-Jun Hou
Summary: Two new maytansinoids were isolated from dried fruits of Trewia nudiflora, with strong cytotoxicity against human tumor cell lines demonstrated.
Review
Biochemistry & Molecular Biology
Svetlana Demyanenko, Valentina Dzreyan, Svetlana Sharifulina
Summary: Cerebral ischemia is the second leading cause of death worldwide, requiring multimodal stroke therapy. Histone deacetylase inhibitors have shown to be effective in protecting the brain from ischemic damage by inducing neurogenesis and angiogenesis in damaged brain areas, promoting functional recovery after stroke.
Article
Chemistry, Medicinal
Yuqi Jiang, Jie Xu, Kairui Yue, Chao Huang, Mengting Qin, Dongyu Chi, Qixin Yu, Yue Zhu, Xiaohan Hou, Tongqiang Xu, Min Li, C. James Chou, Xiaoyang Li
Summary: The study focused on modifying HDAC inhibitors to deactivate the Michael reaction in order to improve their potency. Compound 11h showed significant improvements in both HDAC inhibitory activity and cell-based antitumor assay, demonstrating potential for clinical application and efficacy against AML.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
January M. Watters, Gabriela Wright, Matthew A. Smith, Bijal Shah, Kenneth L. Wright
Summary: The inhibition of HDAC8 can induce apoptosis in MCL cells without affecting the functional activity, receptor expression, or ADCC of NK cells. Additionally, HDAC8 inhibition leads to an increase in IFNγ-producing NK cells.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Agricultural Engineering
Xuefeng Lu, Tae Kyung Hyun
Summary: Post-translational histone modifications, such as histone acetylation, play key roles in regulating gene expression in plant growth, development, and stress responses. The research found that HDAC inhibitors led to hyperacetylation of histone H3, enhancing MeJA-induced ginsenoside production in ginseng adventitious roots. Additionally, the study identified specific PgHDACs that may serve as crucial factors in controlling MeJA-induced ginsenoside production.
INDUSTRIAL CROPS AND PRODUCTS
(2021)
Review
Oncology
Fengyi Guo, Hongjing Wang
Summary: This review summarizes the classification and mechanisms of action of histone deacetylase and the clinical application of their inhibitors in ovarian cancer. Histone deacetylase inhibitors show promising potential as anti-cancer drugs, and combination therapy with other anticancer drugs for synergistic effects can improve efficacy.
FRONTIERS IN ONCOLOGY
(2022)
Article
Chemistry, Medicinal
Ruiqiang Zhang, Hualong Mo, Yan-Yan Ma, Deng-Gao Zhao, Kun Zhang, Tingwen Zhang, Xuecheng Chen, Xi Zheng
Summary: A series of 5-phenyloxazole-2-carboxylic acid derivatives were synthesized and studied for their structure-activity relationships. Compound 9 showed improved cytotoxicity against cancer cells, selectivity for human cancer cells, and was found to inhibit tubulin polymerization leading to cell cycle arrest at G2/M phase. Molecular docking studies revealed that compound 9 bound to the colchicine binding site of tubulin, providing insights for further structural modification of tubulin polymerization inhibitors.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Review
Oncology
Amandine Badie, Christian Gaiddon, Georg Mellitzer
Summary: Our understanding of the identity of many cancers has greatly increased in recent years, leading to progress in early detection and treatment options. However, gastric cancer remains poorly treated with low survival rates. The lack of possibilities for early detection and the variations between tumors of gastric cancer patients are major challenges. Histone Deacetylases (HDACs) have been identified to be potentially related to gastric cancer. In this review, we summarize the current knowledge on the role of HDACs in gastric cancer development and their potential as early detection markers and targets for new treatment options.