A5013849860- Histone Deacetylase Inhibitors Research
- Peptidase Inhibition and Analysis
- Chemical Synthesis and Analysis
- Macrophage Migration Inhibitory Factor
- Parasites and Host Interactions
- HIV/AIDS drug development and treatment
- Protein Degradation and Inhibitors
- Genomics and Chromatin Dynamics
- Asymmetric Hydrogenation and Catalysis
- Cholinesterase and Neurodegenerative Diseases
- RNA Research and Splicing
- Signaling Pathways in Disease
- Physiological and biochemical adaptations
- Microtubule and mitosis dynamics
- Epigenetics and DNA Methylation
- Synthesis and Catalytic Reactions
- RNA and protein synthesis mechanisms
- Trypanosoma species research and implications
- Nitric Oxide and Endothelin Effects
- Erythrocyte Function and Pathophysiology
- Enzyme Production and Characterization
- Enzyme Structure and Function
- Synthetic Organic Chemistry Methods
- Synthesis and biological activity
- Cellular Mechanics and Interactions
Institut de génétique et de biologie moléculaire et cellulaire
2016-2024
Inserm
2016-2024
Université de Strasbourg
2016-2024
Centre National de la Recherche Scientifique
2016-2023
Integrated Structural Biology Grenoble
2021-2022
Institut de Biologie Moléculaire et Cellulaire
2016-2018
Centre for Cellular and Molecular Biology
2015
Council of Scientific and Industrial Research
2013
Schistosomiasis is a major neglected parasitic disease that affects more than 265 million people worldwide and for which the control strategy consists of mass treatment with only available drug, praziquantel. In this study, series new benzohydroxamates were prepared as potent inhibitors Schistosoma mansoni histone deacetylase 8 (smHDAC8). Crystallographic analysis provided insights into inhibition mode smHDAC8 activity by these 3-amidobenzohydroxamates. The newly designed evaluated in...
Metal-dependent histone deacetylases (HDACs) are key epigenetic regulators that represent promising therapeutic targets for the treatment of numerous human diseases. Yet currently FDA-approved HDAC inhibitors nonspecifically target at least several 11 structurally similar but functionally different isozymes, which hampers their broad usage in clinical settings. Selective targeting single isozymes being developed, precise understanding molecular terms selectivity remains sparse. Here, we show...
The phenothiazine system was identified as a favorable cap group for potent and selective histone deacetylase 6 (HDAC6) inhibitors. Here, we report the preparation systematic variation of phenothiazines their analogues containing benzhydroxamic acid moiety zinc-binding group. We evaluated ability to selectively inhibit HDAC6 by recombinant HDAC enzyme assay, determining protein acetylation levels in cells western blotting (tubulin vs acetylation), assessing effects on various cancer cell...
Histone deacetylases (HDACs) are important modulators of epigenetic gene regulation and additionally control the activity non-histone protein substrates. While for HDACs 1–3 6 many potent selective inhibitors have been obtained, other subtypes much less is known on consequences their inhibition. The present report describes development substituted benzhydroxamic acids as HDAC8 inhibitors. Docking studies using available crystal structures used structure-based optimization this series...
A promising means in the search of new small molecules for treatment schistosomiasis (amongst other parasitic ailments) is by targeting epigenome. In present study, a docking based virtual screening procedure using crystal structure histone deacetylase 8 from Schistosoma mansoni (smHDAC8) was designed. From developed protocol, we were able to identify eight novel N-(2,5-dioxopyrrolidin-3-yl)-n-alkylhydroxamate derivatives as smHDAC8 inhibitors with IC50 values ranging 4.4–20.3 µM against...
Abstract Schistosomiasis is a neglected parasitic disease that affects more than 265 million people worldwide and for which the control strategy relies on mass treatment with only one drug: praziquantel. Based 3‐chlorobenzothiophene‐2‐hydroxamic acid J1075 , series of hydroxamic acids different scaffolds were prepared as potential inhibitors Schistosoma mansoni histone deacetylase 8 ( Sm HDAC8). The crystal structures HDAC8 four provided insight into binding mode orientation molecules in...
Abstract Schistosomiasis is a neglected tropical disease caused by parasitic flatworms of the genus Schistosoma , which affects over 200 million people worldwide and leads to at least 300,000 deaths every year. In this study, initial screening revealed triazole‐based hydroxamate 2 b ( N ‐hydroxy‐1‐phenyl‐1 H ‐1,2,3‐triazole‐4‐carboxamide) exhibiting potent inhibitory activity toward novel antiparasitic target mansoni histone deacetylase 8 (smHDAC8) promising selectivity major human HDACs....
Writing and erasing of posttranslational modifications are crucial to phenotypic plasticity antigenic variation eukaryotic pathogens. Targeting pathogens' modification machineries, thus, represents a valid approach fighting parasitic diseases. However, identification targets the development selective anti-parasitic drugs still represent major bottlenecks. Here, we show that zinc-dependent histone deacetylases (HDACs) protozoan parasite Trypanosoma cruzi key regulators have significantly...
Transcription factors, such as nuclear receptors achieve precise transcriptional regulation by means of a tight and reciprocal communication with DNA, where cooperativity gained receptor dimerization is added to binding site sequence specificity expand the range DNA target gene sequences. To unravel evolutionary steps in emergence selection steroid (SRs) from monomeric dimeric palindromic sites, we carried out crystallographic, biophysical phylogenetic studies, focusing on estrogen-related...
Mammalian soluble Guanylate Cyclase (sGC), working as a physiological NO receptor, is investigated using resonance Raman spectroscopy for bound states with different saturation levels in the presence and absence of effectors. The Fe–NO (ν ) N–O N-O stretching bands appeared at 521 1681 cm -1 , respectively, without effectors, but ν was split into 1699 GTP shifted to 1687 YC-1 or BAY 41-2272, while Fe-NO remained unaltered. two were independent levels. YC-1/BAY 41-2272 altered vinyl...
Chromatin structure in eukaryotes and its modulation by epigenetic mechanisms enable the regulation of different nuclear processes. Perturbation can thus affect proper functioning cells, numerous diseases have been linked to deregulation activity effectors human. The reversibility has allowed development "Epigenetic drugs" or "Epidrugs". In a chemical biology approach, we made use importance eukaryotic find drug leads that specifically pathogens responsible for neglected diseases. Our work...