A5008034085- Click Chemistry and Applications
- Histone Deacetylase Inhibitors Research
- HIV/AIDS drug development and treatment
- Cancer therapeutics and mechanisms
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Biochemical and Molecular Research
- Acute Lymphoblastic Leukemia research
- Viral gastroenteritis research and epidemiology
- Reproductive System and Pregnancy
- Tea Polyphenols and Effects
- Tannin, Tannase and Anticancer Activities
- Phytochemicals and Antioxidant Activities
- HIV Research and Treatment
- Melanoma and MAPK Pathways
- Viral Infections and Outbreaks Research
- RNA Interference and Gene Delivery
- Immunotherapy and Immune Responses
- Magnetism in coordination complexes
- Protein Degradation and Inhibitors
- Cytokine Signaling Pathways and Interactions
- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- Animal Virus Infections Studies
- Chronic Lymphocytic Leukemia Research
Centre National de la Recherche Scientifique
2017-2023
Centre de Recherche en Cancérologie de Marseille
2017-2023
Inserm
2017-2023
Institut Paoli-Calmettes
2019
Architecture et Fonction des Macromolécules Biologiques
2015-2018
Aix-Marseille Université
2018
Universidad de Murcia
2006-2014
Cancer cells utilize the main de novo pathway and alternative salvage for deoxyribonucleotide biosynthesis to achieve adequate nucleotide pools. Deoxycytidine kinase is rate-limiting enzyme of it has recently emerged as a target anti-proliferative therapies cancers where essential. Here, we present development potent inhibitor applying an iterative multidisciplinary approach, which relies on computational design coupled with experimental evaluations. This strategy allows acceleration...
CO2 and HCO3− react with the dinuclear hydroxo-complex [Ni(mcN3)(µ-OH)]2(PF6)2 (mcN3 = 2,4,4,9-tetramethyl-1,5,9-triazacyclododec-1-ene) to form µ-CO3 bridged nickel(II) complexes, [{Ni(mcN3)}2(µ-CO3)](PF6)2 (1a) a symmetric core in which both nickel atoms are five-coordinate [Ni(mcN3)(µ-CO3)Ni(mcN3)(MeCN)](PF6)2 (1b) an asymmetric containing five- six-coordinate atoms. The magnetic behaviour indicates existence of antiferromagnetic coupling between metallic centres. A substantial increase...
Background Tumour suppressor genes are often transcriptionally silenced by promoter hypermethylation, and recent research has implicated alterations in chromatin structure as the mechanistic basis for this repression. In addition to DNA methylation, other epigenetic post-translational modifications that modulate stability binding of specific transcription factors gene promoters have emerged important mechanisms controlling expression. The aim study was analyse implications these their...
Dihydrofolate reductase (DHFR) is the subject of intensive investigation since it appears to be primary target enzyme for antifolate drugs. Fluorescence quenching experiments show that ester bond-containing tea polyphenols (-)-epigallocatechin gallate (EGCG) and (-)-epicatechin (ECG) are potent inhibitors DHFR with dissociation constants (KD) 0.9 1.8 μM, respectively, while lacking bound moiety [e.g., (EGC) (EC)] did not bind this enzyme. To avoid stability bioavailability problems...
Masitinib, a highly selective protein kinase inhibitor, can sensitise gemcitabine-refractory cancer cell lines when used in combination with gemcitabine. Here we report reverse proteomic approach that identifies the target responsible for this sensitisation: deoxycytidine (dCK). as well other inhibitors, such imatinib, interact dCK and provoke an unforeseen conformational-dependent activation of nucleoside kinase, modulating phosphorylation analogue drugs. This phenomenon leads to increase...
We recently reported an integrated fragment-based optimization strategy called DOTS (Diversity Oriented Target-focused Synthesis) that combines automated virtual screening (VS) with semirobotized organic synthesis coupled to in vitro evaluation. The molecular modeling part consists of hit-to-lead chemistry, based on the growing paradigm. Here, we have extended applicability by adding new functionalities, allowing a generic chemistry-driven linking approach particular emphasis covalent drugs....
Abstract Despite bioavailability issues, tea catechins have emerged as promising chemopreventive agents because of their efficacy in various animal models. We synthesized two catechin‐derived compounds, 3‐ O ‐(3,4,5‐trimethoxybenzoyl)‐(−)‐catechin (TMCG) and ‐(3,4,5‐trimethoxybenzoyl)‐(−)‐epicatechin (TMECG), an attempt to improve the stability cellular absorption polyphenols. The antiproliferative pro‐apoptotic activities both compounds were analyzed with cancer cell systems, TMCG, which...
Human melanoma is a significant clinical problem. As most patients relapse with lethal drug-resistant disease, understanding and preventing mechanism(s) of resistance one the highest priorities to improve therapy. Melanosomal sequestration cellular exportation cytotoxic drugs have been proposed be important melanoma-specific mechanisms that contribute multidrug in melanoma. Concretely, we found treatment methotrexate (MTX) altered melanogenesis accelerated melanosomes; however, molecular...
The Arenaviridae family, together with the Bunyaviridae and Orthomyxoviridae families, is one of three negative-stranded RNA viral families that encode an endonuclease in their genome. domain at N-terminus L protein, a multifunctional protein includes RNA-dependent polymerase. synthesis mRNA arenaviruses process primed by capped nucleotides are `stolen' from cellular cooperation other domains protein. This molecular mechanism has been demonstrated previously for prototype Lymphocytic...
Abstract The hydroxido complexes [Ni(N 3 ‐mc)(μ‐OH)] 2 [PF 6 ] [N ‐mc = 2,4,4‐trimethyl‐1,5,9‐triazacyclododec‐1‐ene (N ‐mc1) or 2,4,4,9‐tetramethyl‐1,5,9‐triazacyclododec‐1‐ene ‐mc2)] react in the presence of alcohols with CS PhNCS to yield xanthate [(N ‐mc)Ni{S C(OR′)}][PF O ‐alkyl N ‐phenylthiocarbamate ‐mc)Ni{PhNC(OR′)S}][PF complexes; these compounds represent first examples N,S‐chelating thiocarbamates bound nickel(II). reactions thiocarboxylic acids corresponding thiocarboxylate...
Novel tea catechin derivatives have been synthesized, and a structure-activity study, related to the capacity of these other polyphenols bind dihydrofolate reductase (DHFR), has performed. The data showed an effective binding between all molecules free enzyme, dissociation constants synthetic compounds natural analogues were on same order. Polyphenols with configuration better DHFR inhibitors than those epicatechin configuration. Antiproliferative activity was also studied in cultured tumour...
Differentially screening the Fr-PPIChem chemical library on bromodomain and extra-terminal (BET) BRD4-BDII versus -BDI bromodomains led to discovery of a BDII-selective tetrahydropyridothienopyrimidinone (THPTP)-based compound. Structure–activity relationship (SAR) hit-to-lead approaches allowed us develop CRCM5484, potent inhibitor BET proteins with preferential 475-fold selectivity for second BRD3 protein (BRD3-BDII) over its first (BRD3-BDI). Its very low activity was demonstrated in...
<p>Evaluation of in vitro ADME properties and vivo pharmacokinetics EdC.</p>
<p>Supplementary Figure Legends</p>
<p>Sequential steps and intermediates for synthesis of EdC (compound 13).</p>
<p>RNA-seq analysis of T-ALL Jurkat and DLBCL SUDHL-10 after 16-hour treatment with 1µM EdC.</p>
<p>Mutation-based sensitivity patterns and correlation analysis of CRISPR knock-out with EdC sensitivity.</p>
<p>Data collection and refinement statistics of the dCK/UDP/EdC crystal structure.</p>
<p>Additional methods for PRISM screen and EdC synthesis.</p>