The replacement of a phenol group by an aniline or acetanilide group enhances the cytotoxicity of 2-ferrocenyl-1,1-diphenyl-but-1-ene compounds against breast cancer cells

International audienceWe have previously shown that conjugated ferrocenyl p-phenols show strong cytotoxic effects against both the hormone-dependent MCF-7 and hormone-independent MDA-MB-231 breast cancer cell lines, possibly via oxidative quinone methide formation. We now present a series of analogous amine and acetamide compounds: 2-ferrocenyl-1-(4-aminophenyl)-1-phenyl-but-1-ene (Z+E-2), 2-ferrocenyl-1-(4-N-acetylaminophenyl)-1-phenyl-but-1-ene (Z-3), and their corresponding organic molecules 1-(4-aminophenyl)-1,2-bis-phenyl-but-1-ene (Z+E-4) and 1-(4-N-acetamidophenyl)-1,2-bis-phenyl-but-1-ene (Z+E-5). All of the compounds have adequate relative binding affinity values for the estrogen receptor; between 2.8% and 5.7% for ERα, and between 0.18% and 15.5% for ERβ, as well as exothermic ligand binding in in silico ER docking experiments. Compounds 2 and 3 show dual estrogenic/cytotoxic activity on the MCF-7 cell line; they are proliferative at low concentrations (0.1 μM) and antiproliferative at high concentrations (10 μM). On the MDA-MB-231 cell line, the ferrocenyl complexes 2 and 3 are antiproliferative with IC50 values of 0.8 μM for 2 and 0.65 μM for 3, while the purely organic molecules 4 and 5 show no effect. Electrochemical experiments suggest that both 2 and 3 can be transformed to oxidized quinoid-type species, analogous to what had previously been observed for the ferrocene phenols

The replacement of a phenol group by an aniline or acetanilide group enhances the cytotoxicity of 2-ferrocenyl-1,1-diphenyl-but-1-ene compounds against breast cancer cells

International audienceWe have previously shown that conjugated ferrocenyl p-phenols show strong cytotoxic effects against both the hormone-dependent MCF-7 and hormone-independent MDA-MB-231 breast cancer cell lines, possibly via oxidative quinone methide formation. We now present a series of analogous amine and acetamide compounds: 2-ferrocenyl-1-(4-aminophenyl)-1-phenyl-but-1-ene (Z+E-2), 2-ferrocenyl-1-(4-N-acetylaminophenyl)-1-phenyl-but-1-ene (Z-3), and their corresponding organic molecules 1-(4-aminophenyl)-1,2-bis-phenyl-but-1-ene (Z+E-4) and 1-(4-N-acetamidophenyl)-1,2-bis-phenyl-but-1-ene (Z+E-5). All of the compounds have adequate relative binding affinity values for the estrogen receptor; between 2.8% and 5.7% for ERα, and between 0.18% and 15.5% for ERβ, as well as exothermic ligand binding in in silico ER docking experiments. Compounds 2 and 3 show dual estrogenic/cytotoxic activity on the MCF-7 cell line; they are proliferative at low concentrations (0.1 μM) and antiproliferative at high concentrations (10 μM). On the MDA-MB-231 cell line, the ferrocenyl complexes 2 and 3 are antiproliferative with IC50 values of 0.8 μM for 2 and 0.65 μM for 3, while the purely organic molecules 4 and 5 show no effect. Electrochemical experiments suggest that both 2 and 3 can be transformed to oxidized quinoid-type species, analogous to what had previously been observed for the ferrocene phenols

OWL Model of Clinical Trial Eligibility Criteria Compatible With Partially-known Information

Abstract. Clinical trials are important for patients, for researchers and for companies. One of the major bottlenecks is patient recruitment. This task requires to match a great quantity of information about the patient with numerous eligibility criteria, in a logically-complex combination. Moreover, the patient’s information required by some of the eligibility criteria may not be available at the time of pre-screening. In such situations, the classic approach based on negation as failure ignores the distinction between a trial for which patient eligibility should be rejected and trials for which patient eligibility cannot be asserted, which resuls in underestimating recruitment. We propose an OWL design pattern for modeling eligibility criteria based on the open world assumption to address the missing information problem

The holobiont, a biological lever to manage some declines of grapevine

International audienceThe concept of a multicellular organism to describe complex organisms composed of groups of analogous cells called tissues and organs with specific functions, shows currently some limitations. An organism such as a plant does not live alone, but closely associated with different microbial communities making up its microbiomes. The microbiomes, specific to a tissue, interact with the plant and modulate some of its functions, including physiology and immunity. The host and the associated microbiomes define a holobiont, whose function is influenced by the spatio-temporal dynamics of their interactions. Thus, a dysfunction of the grapevine holobiont (linked for example to inappropriate technical itineraries or to climate change) could lead to the development of diseases or physiological disorders, similarly to the alteration of gut microbiota observed in numerous human diseases as type 2 diabetes, obesity and irritable bowel syndrome. The analysis of microbial communities associated with a plant such as grapevine has until recently been limited by the fact that most microorganisms cannot be cultured in vitro. New methods (named -omics) based on the analysis of genome, metabolome and proteome allow to define the taxonomic and functional characteristics of the different microbiomes associated with a plant, in particular organisms (i.e. bacteria, fungi) that are not cultivable. In the Holoviti project, we aim to characterize the role of microbiomes in grapevine homeostasis by describing and comparing the holobiont of i) healthy grapevines and ii) grapevines affected by three declines (Esca / BDA, fanleaf and linked to 161-49C rootstock). One of our objectives is to identify taxonomic and functional bio-indicators (linked to either microbes or the plant) of the host sanitary status. One prospect could be handle the microbial component of the holobiont to improve some ecosystemic services, such as the control of pathogens or the fight against abiotic stresses

L’holobionte vigne, un levier biologique pour lutter contre les dépérissements ?

National audienc

L’holobionte « vigne » face au dépérissement ou quand le « vivre ensemble » n’est plus à l’équilibre

Prod 2019-165 SPE EA IPM BIOmE GenoSol INRA UBNational audienc