ArticleJournal of medicinal chemistry2019
Synthesis and Biological Investigation of Phenothiazine-Based Benzhydroxamic Acids as Selective Histone Deacetylase 6 Inhibitors.
Article in Journal of medicinal chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 100 citations in OpenAlex.
- Synthesis of 2-Aryl(alkyl)benzimidazole Hydroxamic Acids as HDAC Inhibitors with Anti-Angiogenesis Properties.ChemMedChem · 2026Article
- New 1,2,3-Triazole and Dipyridothiazine Hybrids-Synthesis, Analysis, Cytotoxicity and Molecular Docking.Biomolecules · 2026Article
- Design, Synthesis, Analysis, and Cytotoxicity of Novel Heteroaryl Derivatives of Dipyridothiazines.Current issues in molecular biology · 2026Article
- Intepirdine Derivatives Possessing Dual 5HT6 Antagonism / HDAC6 Inhibitory Activity.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Serendipitous and Systematic Chemoproteomic Discovery of MBLAC2, HINT1, and NME1-4 Inhibitors from Histone Deacetylase-Targeting Pharmacophores.ACS chemical biology · 2025Article
- Discovery of Novel Imidazothiazole-Based Hydroxamic Acid Derivatives as Potent Indoleamine 2,3-Dioxygenase 1 and Histone Deacetylase 6 Dual Inhibitors.Molecules (Basel, Switzerland) · 2025Article
- Enhancing HDAC Inhibitor Screening: Addressing Zinc Parameterization and Ligand Protonation in Docking Studies.International journal of molecular sciences · 2025Article
- Design, synthesis, biological andBiomedical reports · 2025Article
- Synthesis and biological evaluation ofJournal of enzyme inhibition and medicinal chemistry · 2024Article
- Recent advances in Alzheimer's disease: Mechanisms, clinical trials and new drug development strategies.Signal transduction and targeted therapy · 2024Review
- Chemical Versatility in Catalysis and Inhibition of the Class IIb Histone Deacetylases.Accounts of chemical research · 2024Review
- Comparative Structure-Based Virtual Screening Utilizing Optimized AlphaFold Model Identifies Selective HDAC11 Inhibitor.International journal of molecular sciences · 2024Article
- Development of First-in-Class Dual Sirt2/HDAC6 Inhibitors as Molecular Tools for Dual Inhibition of Tubulin Deacetylation.Journal of medicinal chemistry · 2023Article
- Divergent access to 5,6,7-perifused cycles.Nature communications · 2023Article
- Design, Synthesis, and Biological Evaluation of Novel Quinazolin-4(3H)-One-Based Histone Deacetylase 6 (HDAC6) Inhibitors for Anticancer Activity.International journal of molecular sciences · 2023Article
- Discovery of Benzylpiperazine Derivatives as CNS-Penetrant and Selective Histone Deacetylase 6 Inhibitors.ACS medicinal chemistry letters · 2022Article
- Identification of histone deacetylase inhibitors with (arylidene)aminoxy scaffold active in uveal melanoma cell lines.Journal of enzyme inhibition and medicinal chemistry · 2021Article
- Harnessing sulfur and nitrogen in the cobalt(iii)-catalyzed unsymmetrical double annulation of thioamides: probing the origin of chemo- and regio-selectivity.Chemical science · 2021Article
- Structural and in Vivo Characterization of Tubastatin A, a Widely Used Histone Deacetylase 6 Inhibitor.ACS medicinal chemistry letters · 2020Article
- Structural determinants of affinity and selectivity in the binding of inhibitors to histone deacetylase 6.Bioorganic & medicinal chemistry letters · 2020Review
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
The phenothiazine system was identified as a favorable cap group for potent and selective histone deacetylase 6 (HDAC6) inhibitors. Here, we report the preparation and systematic variation of phenothiazines and their analogues containing a benzhydroxamic acid moiety as the zinc-binding group. We evaluated their ability to selectively inhibit HDAC6 by a recombinant HDAC enzyme assay, by determining the protein acetylation levels in cells by western blotting (tubulin vs histone acetylation), and by assessing their effects on various cancer cell lines. Structure-activity relationship studies revealed that incorporation of a nitrogen atom into the phenothiazine framework results in increased potency and selectivity for HDAC6 (more than 500-fold selectivity relative to the inhibition of HDAC1, HDAC4, and HDAC8), as rationalized by molecular modeling and docking studies. The binding mode was confirmed by co-crystallization of the potent azaphenothiazine inhibitor with catalytic domain 2 from Danio rerio HDAC6.
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Registered trials
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