A5039009881- Quinazolinone synthesis and applications
- Synthesis and Characterization of Heterocyclic Compounds
- Synthesis and biological activity
- Synthesis and Reactivity of Heterocycles
- Biochemical and Molecular Research
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Bioactive Compounds and Antitumor Agents
- Genetics and Neurodevelopmental Disorders
- Down syndrome and intellectual disability research
- 14-3-3 protein interactions
- Cancer-related Molecular Pathways
- RNA and protein synthesis mechanisms
- Cancer therapeutics and mechanisms
- Cystic Fibrosis Research Advances
- Chronic Lymphocytic Leukemia Research
- Mitochondrial Function and Pathology
- Alkaloids: synthesis and pharmacology
- Cell death mechanisms and regulation
- Viral-associated cancers and disorders
- RNA modifications and cancer
- Synthesis and bioactivity of alkaloids
- Congenital heart defects research
- Cancer Mechanisms and Therapy
- RNA Research and Splicing
Établissement Français du Sang
2018-2025
Centre Hospitalier Régional Universitaire de Brest
2018-2023
Brest State A.S. Pushkin University
2023
Université de Bretagne Occidentale
2018-2023
Inserm
2014-2023
Station Biologique de Roscoff
2012-2020
ManRos Therapeutics (France)
2012-2019
École nationale d'ingénieurs de Brest
2019
Centre National de la Recherche Scientifique
2013-2017
Université Claude Bernard Lyon 1
2014-2017
The protein kinase DYRK1A has been suggested to act as one of the intracellular regulators contributing neurological alterations found in individuals with Down syndrome. For an assessment role DYRK1A, selective synthetic inhibitors are valuable pharmacological tools. However, described literature so far either not sufficiently or have tested against closely related kinases from DYRK and CLK families. aim this study was identification exhibiting selectivity versus structurally functionally...
Growing evidence supports the implication of DYRK1A in development cognitive deficits seen Down syndrome (DS) and Alzheimer's disease (AD). We here demonstrate that pharmacological inhibition brain is able to correct recognition memory three DS mouse models with increasing genetic complexity [Tg(Dyrk1a), Ts65Dn, Dp1Yey], all expressing an extra copy Dyrk1a Overexpressed accumulates cytoplasm at synapse. Treatment inhibitor leucettine L41 leads normalization activity corrects novel object...
Significance Historically, pulmonary infections treated with antibiotics killed bacteria while selecting for the unintended development of pathogenic resistance. One strategy to circumvent antibiotic resistance in infection involves targeting host phagosome and augmenting its function. To such an end, we have identified several small molecules, (R)-roscovitine derivatives, which restore microbicidal activity compromised alveolar macrophages cystic fibrosis (CF) enhance function non-CF cells....
Neuroblastoma (NB), the most frequent extracranial solid tumor of children accounting for nearly 15% all childhood cancer mortality, displays overexpression antiapoptotic Bcl-2 and Mcl-1 in aggressive forms disease. The clinical phase 2 drug roscovitine (CYC202, seliciclib), a relatively selective inhibitor cyclin-dependent kinases (CDKs), CR8, recently developed more potent analog, induce concentration-dependent apoptotic cell death NB cells (average IC50 values: 24.2 µM 0.4 respectively)....
The total synthesis of the optically active (aR)- and (aS)-16-methyllamellarins N (3a 3b) was achieved via resolution on HPLC chiral stationary phase. kinase inhibitory activities both enantiomers were evaluated eight protein kinases relevant to cancer neurodegenerative diseases (CDK1/cyclin B, CDK2/cyclin A, CDK5/p25, GSK-3α/β, PIM1, DYRK1A, CLK3, CK1). Isomer (aR)-3b exhibited potent but nonselective inhibition all except CK1, while (aS)-3a selectively inhibited only DYRK1A. different...
Two new acridone alkaloids, chlorospermines A and B (1 2), were isolated from the stem bark of Glycosmis chlorosperma, together with known atalaphyllidine (3) acrifoline (4), by means bioguided isolation using an in vitro enzyme assay against DYRK1A. Acrifoline (4) to a lesser extent chlorospermine (2) showed significant inhibiting activity on DYRK1A IC50's 0.075, 5.7, 2.2 μM, respectively. Their selectivity profile was evaluated panel various kinases, molecular docking calculations provided...
Abstract Identifying dosage-sensitive genes is a key to understand the mechanisms underlying intellectual disability in Down syndrome (DS). The Dp(17Abcg1-Cbs)1Yah DS mouse model (Dp1Yah) shows cognitive phenotypes that need be investigated identify main genetic driver. Here, we report three copies of cystathionine-beta-synthase gene (Cbs) Dp1Yah mice are necessary observe deficit novel object recognition (NOR) paradigm. Moreover, overexpression Cbs alone sufficient induce deficits NOR test....
The convenient synthesis of a library novel 6,6,5-tricyclic thiazolo[5,4-f] quinazolines (forty molecules) was achieved mainly under microwave irradiation. Dimroth rearrangement and 4,5-dichloro-1,2,3,-dithiazolium chloride (Appel salt) chemistry were associated for the 6-aminobenzo[d]thiazole-2,7-dicarbonitrile (16) versatile molecular platform various bioactive derivatives. Kinase inhibition final compounds evaluated on panel four Ser/Thr kinases (DYRK1A, CDK5, CK1 GSK3) chosen their...
BCL-x is a master regulator of apoptosis whose pre-mRNA alternatively spliced into either long (canonical) anti-apoptotic Bcl-xL isoform, or short (alternative) pro-apoptotic Bcl-xS isoform. The balance between these two antagonistic isoforms tightly regulated and overexpression has been linked to resistance chemotherapy in several cancers, whereas associated some forms diabetes cardiac disorders. splicing factor RBM25 controls alternative BCL-x: its favours the production Bcl-xS,...
Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is a potential drug target because of its role in the development Down syndrome and Alzheimer's disease. The selective DYRK1A inhibitor 10-iodo-11H-indolo[3,2-c]quinoline-6-carboxylic acid (KuFal194), large, flat lipophilic molecule, suffers from poor water solubility, limiting use as chemical probe cellular assays animal models. Based on structure KuFal194, 7-chloro-1H-indole-3-carbonitrile was selected fragment template...
Abstract The copper ionophore disulfiram (DSF) is commonly used to treat chronic alcoholism and has potential anti-cancer activity. Using a yeast-based screening assay of FDA-approved compounds, DSF was herein identified for its ability improve oxidative phosphorylation-dependent growth various yeast models mitochondrial diseases caused by wide range defects in ATP synthase, complexes III IV, cardiolipin remodeling, maintenance translation the genome. This compound also showed beneficial...
Seven new adociaquinone derivatives, xestoadociaquinones A (1a), B (1b), 14-carboxy-xestoquinol sulfate (2) and xestoadociaminals A–D (3a, 3c, 4a, 4c), together with seven known compounds (5–11) were isolated from an Indonesian marine sponge Xestospongia sp. Their structures elucidated by extensive 1D 2D NMR mass spectrometric data. All the evaluated for their potential inhibitory activity against eight different protein kinases involved in cell proliferation, cancer, diabetes...
Glioblastomas are the most frequent and aggressive primary brain tumors in adults. The median overall survival is limited to a few months despite surgery, radiotherapy, chemotherapy. It now clearly established that hyperactivity of cyclin-dependent kinases (CDKs) one processes underlying hyperproliferation tumoral growth. marine natural products meridianins variolins, characterized as CDK inhibitors, display kinase-inhibitory activity associated with cytotoxic effects. In order improve...
Since hyperactivity of the protein kinase DYRK1A is linked to several neurodegenerative disorders, inhibitors have been suggested as potential therapeutics for Down syndrome and Alzheimer's disease. Most published date suffer from low selectivity against related kinases or unfavorable physicochemical properties. In order identify with improved properties, a series new chemicals based on [b]-annulated halogenated indoles were designed, synthesized, evaluated biological activity. Analysis...