Les composés néoformés toxiques et leur remédiation - Focus sur les produits carnés

Ce numéro est constitué d’articles issus du colloque « Contaminants alimentaires – approches émergentes pour connaître et prévenir le risque » qui s’est tenu à Paris le 19 décembre 2018.Food processing induces chemical reactions that can lead to the formation of process-induced toxicants which will in turn impact the food safety. These reactions are dependent on several factors including the composition of the raw material and the processing conditions. Although process-induced toxicants are generally produced at trace level, the consumer is exposed to them frequently and throughout his life. They may therefore contribute to the development of some pathologies including diabetes, cancer and neurological disorders. In most cases, they are generated by the consumer when he prepares his food, which makes it difficult to assess exposure levels and the risks associated with their ingestion. Currently, very few process-induced toxicants (e.g. acrylamide, benzo[a]pyrene, monochloropropane diol) are regulated in our diet. Recent advances in analytical techniques and reaction chemistry now allow a better knowledge of these compounds, their conditions of formation, and pave the way to solutions to mitigate them.Les procédés de transformation induisent des réactions chimiques au sein des aliments pouvant amener à la formation de composés néoformés toxiques. Ces néoformations qui dépendent entre autres de la composition de la matière première et des conditions de procédé peuvent impacter la qualité sanitaire des aliments. Bien que les composés néoformés toxiques soient généralement retrouvés à l’état de trace dans les aliments, leur consommation régulière tout au long de la vie pourrait contribuer à terme au développement de certaines pathologies (diabète, cancers, troubles neurologiques…). Souvent générés par le consommateur lors de la préparation domestique de ses aliments, l’évaluation des niveaux d’exposition et donc des risques liés à leur ingestion est complexe. A l’heure actuelle, très peu de composés néoformés sont réglementés dans notre alimentation (acrylamide, benzo[a]pyrène, monochloropropane diol). Les progrès récents en matière de techniques d’analyse et de chimie réactionnelle permettent aujourd’hui une meilleure connaissance de ces composés, de leurs conditions de formation et ouvrent la voie à des solutions pour y remédier

Hazard control through processing and preservation technologies for enhancing the food safety management of infant food chains

Food safety of infant foods is of paramount importance due to the high vulnerability of this population. Food business operators guarantee safety of the products they put on the market by implementing control measures that prevent, eliminate, reduce, or keep relevant physical, microbiological and/or chemical hazards to an acceptable level. It is essential that the efficacy of control measures is validated during process design and on-line monitoring and periodic verification activities are implemented during the commercial production. Infant foods are usually processed through conservative thermal treatments that guarantee food safety but usually negatively affect the organoleptic properties, reduce vitamin and nutrient contents. Heat treatments can trigger the formation of process induced contaminants.The EU-SAFFI project aims to set and validate new/emerging processing and preservation technologies (i.e. pulse combustion drying, radiofrequency and high pressure processing) to control key contaminants and pathogens as efficiently as classical technologies and to provide a decision support system to manage food safety in infant food. This article describes how the project is addressing the research to control (i) furan, a key process-induced toxicant in infant food whose formation is induced during thermal preservation processes of foods such as infant formulas and jarred baby foods, (ii) tropane alkaloids, natural contaminants found in agricultural crops due to accidental harvesting of weeds whose presence above the maximum regulated levels have been documented in cereal-based foods for infants and children and (iii) different vegetative and spore forming bacterial pathogens, a group of microbiological hazards with product and technology-specific relevance and resistance.info:eu-repo/semantics/publishedVersio

Structural Insights into the Inhibition of Cytosolic 5′-Nucleotidase II (cN-II) by Ribonucleoside 5′-Monophosphate Analogues

Cytosolic 5′-nucleotidase II (cN-II) regulates the intracellular nucleotide pools within the cell by catalyzing the dephosphorylation of 6-hydroxypurine nucleoside 5′-monophosphates. Beside this physiological function, high level of cN-II expression is correlated with abnormal patient outcome when treated with cytotoxic nucleoside analogues. To identify its specific role in the resistance phenomenon observed during cancer therapy, we screened a particular class of chemical compounds, namely ribonucleoside phosphonates to predict them as potential cN-II inhibitors. These compounds incorporate a chemically and enzymatically stable phosphorus-carbon linkage instead of a regular phosphoester bond. Amongst them, six compounds were predicted as better ligands than the natural substrate of cN-II, inosine 5′-monophosphate (IMP). The study of purine and pyrimidine containing analogues and the introduction of chemical modifications within the phosphonate chain has allowed us to define general rules governing the theoretical affinity of such ligands. The binding strength of these compounds was scrutinized in silico and explained by an impressive number of van der Waals contacts, highlighting the decisive role of three cN-II residues that are Phe 157, His 209 and Tyr 210. Docking predictions were confirmed by experimental measurements of the nucleotidase activity in the presence of the three best available phosphonate analogues. These compounds were shown to induce a total inhibition of the cN-II activity at 2 mM. Altogether, this study emphasizes the importance of the non-hydrolysable phosphonate bond in the design of new competitive cN-II inhibitors and the crucial hydrophobic stacking promoted by three protein residues

Les composés néoformés toxiques et leur remédiation - Focus sur les produits carnés

Les procédés de transformation induisent des réactions chimiques au sein des aliments pouvant amener à la formation de composés néoformés toxiques. Ces néoformations qui dépendent entre autres de la composition de la matière première et des conditions de procédé peuvent impacter la qualité sanitaire des aliments. Bien que les composés néoformés toxiques soient généralement retrouvés à l’état de trace dans les aliments, leur consommation régulière tout au long de la vie pourrait contribuer à terme au développement de certaines pathologies (diabète, cancers, troubles neurologiques…). Souvent générés par le consommateur lors de la préparation domestique de ses aliments, l’évaluation des niveaux d’exposition et donc des risques liés à leur ingestion est complexe. A l’heure actuelle, très peu de composés néoformés sont réglementés dans notre alimentation (acrylamide, benzo[a]pyrène, monochloropropane diol). Les progrès récents en matière de techniques d’analyse et de chimie réactionnelle permettent aujourd’hui une meilleure connaissance de ces composés, de leurs conditions de formation et ouvrent la voie à des solutions pour y remédier.Food processing induces chemical reactions that can lead to the formation of process-induced toxicants which will in turn impact the food safety. These reactions are dependent on several factors including the composition of the raw material and the processing conditions. Although process-induced toxicants are generally produced at trace level, the consumer is exposed to them frequently and throughout his life. They may therefore contribute to the development of some pathologies including diabetes, cancer and neurological disorders. In most cases, they are generated by the consumer when he prepares his food, which makes it difficult to assess exposure levels and the risks associated with their ingestion. Currently, very few process-induced toxicants (e.g. acrylamide, benzo[a]pyrene, monochloropropane diol) are regulated in our diet. Recent advances in analytical techniques and reaction chemistry now allow a better knowledge of these compounds, their conditions of formation, and pave the way to solutions to mitigate them

Xénobiotiques et Néoformés

National audienc

Synthèse et étude d'inhibiteurs potentiels de la 5'-nucléotidase cytosolique II (Analogues de mononucléotides en série phosphonate et leurs prodrogues)

Les analogues de nucléosides représentent une famille d'agents thérapeutiques très largement utilisée en chimiothérapie anticancéreuse. Cependant, des phénomènes de résistance d'origine multifactorielle apparaissent et il semble que la surexpression d'une enzyme, la 5'-nucléotidase cytosolique II (cN-II) soit un des facteurs impliqués. Nous nous sommes donc intéressés à son étude ainsi qu'à la synthèse d'inhibiteurs potentiels de type analogues de nucléosides phosphonates modifiés en position á/â. Ce manuscrit rapporte dans un premier temps aux particularités de la cN-II puis l'élaboration d'un test d'évaluation efficace. Suite à la mise en oeuvre de différentes techniques d'enzymologie, le dosage colorimétrique au vert de Malachite a été retenu. Le second chapitre décrit l'optimisation et la synthèse d'analogues de type alcyne phosphonate selon deux approches puis l'évaluation de leur capacité à inhiber la cN-II. La troisième partie traite d'une nouvelle approche synthétique de nucléosides phosphonates â-modifiés via l'utilisation d'un intermédiaire â-cétophosphonate. Des dérivés de type â-hydroxyphosphonate et â-oximephosphonate ont été obtenus et testés. Enfin, la mise au point d'une stratégie inédite pour la synthèse de prodrogues bisSATE de â-hydroxyphosphonates (têtes de série) via l'ouverture d'un époxyde par un phosphite a été réaliséeNucleosidic analogs are widely used as therapeutic agents in antitumoral chemotherapy. However, cellular resistance appears in a multifactorial manner and it seems that overexpression of an enzyme, the 5'-cytosolic nucleotidase (cN-II) may be involved in this phenomenon. We were interested in the study of this enzyme in order to design and synthesize potential inhibitors belonging to the family of nucleoside analogs in the á/â-modified phosphonate series. First, we reviewed literature data on the nucleotidase family and particularly on cN-II, then we engaged in the setting up of an evaluation test using various enzymological techniques. Thus, green malachite colorimetric assay was successful and efficient for the evaluation of the inhibitor capacity of our different derivatives. Secondly, we described the optimisation and the synthesis of alkynylphosphonate nucleoside analogs using two different pathways. These latter were tested and the cytosine analog inhibited 65% of the enzyme activity. Then, a new synthetic approach to â-modified nucleoside phosphonates was reported using a â-ketophosphonate as key intermediate. â-hydroxyphosphonate et â-oximephosphonate analogs were obtained and inhibited 50% of the enzyme activity. Finally, a novel prodrug stategy for the synthesis of bisSATE ester of â-hydroxyphosphonates (our leading series) was designed and developpedMONTPELLIER-BU Sciences (341722106) / SudocSudocFranceF

5.11. Les produits néoformés*

Les procédés de transformation des aliments induisent la formation de constituants désignés comme « néoformés » et susceptibles de moduler leurs qualités sanitaires, nutritionnelles et organoleptiques. Certains composés néoformés affectent la sécurité chimique du fait de leur cancérogénicité, mutagénicité ou neurotoxicité. Ils peuvent être générés lors de la cuisson, de la digestion ou au contact d’emballages. Les autorités sanitaires leur portent une attention croissante et ciblent notamment..

Synthesis of pyrimidine containing nucleoside β-(R/S)-hydroxyphosphonate analogues

A concise route to nucleoside β-hydroxyphosphonate analogues is described. The use of a nucleoside β-ketophosphonate as the key intermediate allowed both the (R) and (S) isomers of β-hydroxyphosphonate analogues in the pyrimidine series to be accessed. Such derivatives may be considered as stable mimics of 5′-monophosphate nucleosides and, therefore, could be the starting point for the development of potential therapeutic agents