Review
Biochemistry & Molecular Biology
Anton Fruhauf, Franz-Josef Meyer-Almes
Summary: HDACs play a role in many diseases, and the hydroxamate group in HDACis may cause toxic side effects, leading to exploration of non-hydroxamic HDACis. These new inhibitors have alternative ZBGs to replace the hydroxamate group, maintaining high potency and high selectivity.
Editorial Material
Microbiology
Tom Boissavy, Dante Rotili, Thomas Mouveaux, Emmanuel Roger, El Moukthar Aliouat, Christine Pierrot, Sergio Valente, Antonello Mai, Mathieu Gissot
Summary: Toxoplasmosis is a significant health issue for immune-deficient individuals and newborns of infected mothers. New compounds with potent anti-parasitic activity have been discovered, which can serve as therapeutic targets for the treatment of toxoplasmosis.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
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
Biochemistry & Molecular Biology
Saravanan Kandasamy, Manikandan Selvaraj, Karthikeyan Muthusamy, Naveena Varadaraju, Srinivasan Kannupal, Ashok Kumar Sekar, Ravikumar Vilwanathan
Summary: HDAC inhibitors are a new class of cancer chemotherapeutics that restore acetylation balance and inhibit HDAC enzymes. Berberine is a pan inhibitor for HDAC, but isoform specific inhibition is still needed. Through structural modification, we obtained berberine derivatives that showed better inhibition of HDAC enzymes and improved clinical efficacy.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
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
Chemistry, Medicinal
Negar Omidkhah, Razieh Ghodsi
Summary: NO-HDAC dual inhibitors have demonstrated satisfactory therapeutic effects in various diseases and possess high therapeutic potential.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Eva Hesping, Ming Jang Chua, Marc Pflieger, Yunan Qian, Lilong Dong, Prabhakar Bachu, Ligong Liu, Thomas Kurz, Gillian M. Fisher, Tina S. Skinner-Adams, Robert C. Reid, David P. Fairlie, Katherine T. Andrews, Alain-Dominique J. P. Gorse
Summary: Malaria, a deadly disease caused by Plasmodium parasites, claims a large number of lives every year. Due to the increasing resistance of the parasites to current antimalarials, there is a need for new drugs. Researchers have developed quantitative structure-activity relationship models to predict the antiplasmodial activity of hydroxamate-based HDAC inhibitors and identified three compounds with strong activity against the parasites.
ACS INFECTIOUS DISEASES
(2022)
Article
Oncology
Roisin M. Connolly, Fengmin Zhao, Kathy D. Miller, Min-Jung Lee, Richard L. Piekarz, Karen L. Smith, Ursa A. Brown-Glaberman, Jennifer S. Winn, Bryan A. Faller, Adedayo A. Onitilo, Mark E. Burkard, George T. Budd, Ellis G. Levine, Melanie E. Royce, Peter A. Kaufman, Alexandra Thomas, Jane B. Trepel, Antonio C. Wolff, Joseph A. Sparano
Summary: The combination of entinostat and exemestane did not improve survival in patients with AI-resistant advanced HR-positive, HER2-negative breast cancer. E2112 phase III trial: no benefit seen in adding HDAC inhibitor entinostat to exemestane in advanced breast cancer.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Chemistry, Medicinal
Dimitrios Triantafyllos Gerokonstantis, Christiana Mantzourani, Dimitrios Gkikas, Kai-Chen Wu, Huy N. Hoang, Ierasia Triandafillidi, Ilianna Barbayianni, Paraskevi Kanellopoulou, Alexandros C. Kokotos, Panagiota Moutevelis-Minakakis, Vassilis Aidinis, Panagiotis K. Politis, David P. Fairlie, George Kokotos
Summary: Benzamides, as HDAC inhibitors, have shown promising anticancer activity and potential for treating fibrotic disorders.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Pharmacology & Pharmacy
Yvonne E. Klingl, Donya Pakravan, Ludo Van den Bosch
Summary: ALS is a devastating neurodegenerative disease with limited treatment options. Research suggests that interference with histone deacetylases may be helpful in treating ALS.
BRITISH JOURNAL OF PHARMACOLOGY
(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
Biochemical Research Methods
Kavinda E. Herath, Ishadi K. M. Kodikara, Mary Kay H. Pflum
Summary: HDAC1 plays a key role in diverse cellular processes and its aberrant expression is linked to many diseases. Nonhistone substrates of HDAC1 have been discovered, revealing its diverse roles beyond epigenetics. We tested the robustness of HDAC1 substrate trapping with multiple mutants and found that using a single mutant yielded more biologically interesting hits. Carnosine N-methyltransferase 1 (CARNMT1) was validated as an HDAC1 substrate. Mutant trapping is an effective method for discovering unanticipated HDAC substrates and linking HDAC activity to unexpected biological functions.
JOURNAL OF PROTEOMICS
(2023)
Article
Chemistry, Multidisciplinary
Yingjun Li, Yongjun Huang, Huimin Cheng, Fang Xu, Ruxi Qi, Botao Dai, Yujian Yang, Zhengchao Tu, Lijie Peng, Zhang Zhang
Summary: In this study, a series of novel dual inhibitors of BRAF and HDACs were designed and synthesized, and compound 14b was found to possess potent activities against BRAF and HDACs, inhibiting cell proliferation effectively. These results support the further development of compound 14b as a promising lead molecule and its use as a tool for studying the effects of BRAF/HDAC dual inhibitors.
FRONTIERS IN CHEMISTRY
(2022)
Review
Medicine, General & Internal
Lorenz Gerbeth, Rainer Glauben
Summary: Inflammatory bowel diseases are severe conditions of the gastrointestinal tract associated with defects in epithelial cell function. Current therapeutic approaches focus on targeting immune cell signaling to alleviate symptoms. The protein family of histone deacetylases (HDACs) has gained attention as potential therapeutic targets for these conditions.
FRONTIERS IN MEDICINE
(2021)
Article
Chemistry, Physical
Negar Omidkhah, Farzin Hadizadeh, Khalil Abnous, Razieh Ghodsi
Summary: A series of quinoline-based benzamide derivatives were designed and synthesized as HDAC inhibitors and anticancer agents. The synthesized compounds showed cytotoxic activity against several human cancer cell lines, with the highest cytotoxicity observed in colorectal cancer and lung cancer cells. Compounds with a methyl group at position 2 of the quinoline ring exhibited better cytotoxicity compared to those with an aryl group. The most potent cytotoxic compounds also displayed strong enzyme inhibitory activity.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Chemistry, Medicinal
Eleni Pontiki, Dimitra Hadjipavlou-Litina, Alexandros Patsilinakos, Trang M. Tran, Charles M. Marson
FUTURE MEDICINAL CHEMISTRY
(2015)
Article
Chemistry, Medicinal
Charles M. Marson, Christopher J. Matthews, Stephen J. Atkinson, Nermina Lamadema, N. Shaun B. Thomas
JOURNAL OF MEDICINAL CHEMISTRY
(2015)
Article
Chemistry, Organic
Charles M. Marson, Kin Cheung Yau
Article
Chemistry, Organic
Jonathan A. Dines, Charles M. Marson
Article
Chemistry, Multidisciplinary
Rossella Promontorio, Jean-Alexandre Richard, Charles M. Marson
Article
Oncology
Chuay-Yeng Koo, Caterina Giacomini, Marta Reyes-Corral, Yolanda Olmos, Ignatius A. Tavares, Charles M. Marson, Spiros Linardopoulos, Andrew N. Tutt, Jonathan D. H. Morris
MOLECULAR CANCER THERAPEUTICS
(2017)
Article
Chemistry, Organic
Rossella Promontorio, Jean-Alexandre Richard, Charles M. Marson
TETRAHEDRON LETTERS
(2018)
Letter
Hematology
Lenushka Maharaj, Charles M. Marson, Brian J. Middleton, Alf S. Rioja, Jackie Perry, Heather Oakervee, Jamie Cavenagh, Simon P. Joel, Rakesh Popat
BRITISH JOURNAL OF HAEMATOLOGY
(2013)
Review
Chemistry, Multidisciplinary
Charles M. Marson
Review
Chemistry, Multidisciplinary
Charles M. Marson
CHEMICAL SOCIETY REVIEWS
(2011)
Review
Chemistry, Multidisciplinary
Charles M. Marson
CHEMICAL SOCIETY REVIEWS
(2012)
Article
Cell Biology
E. S. K. Assem, S. Mann, B. Y. C. Wan, C. M. Marson
INFLAMMATION RESEARCH
(2010)
Article
Chemistry, Medicinal
Charles M. Marson, Christopher J. Matthews, Elena Yiannaki, Stephen J. Atkinson, Peter E. Soden, Lena Shukla, Nermina Lamadema, N. Shaun B. Thomas
JOURNAL OF MEDICINAL CHEMISTRY
(2013)
Article
Chemistry, Organic
Mehrnoosh Ostovar, Charles M. Marson
Article
Biochemistry & Molecular Biology
Patrizia Ferretti, Kin U. Pong, Barbora Vagaska, Rohan Merchant, Christopher J. Matthews, Charles M. Marson