Proteins of the Bcl-2 family are key targets in anticancer drug discovery. Disrupting the interaction between anti- and pro-apoptotic members of this protein family was the approach chosen in this study to restore apoptosis. Thus, a biological screening on the modulation of the Bcl-xL/Bak and Mcl-1/Bid interactions permitted the selection of Knema hookeriana for further phytochemical investigations. The ethyl acetate extract from the stem bark led to the isolation of six new compounds, three acetophenone derivatives (1-3) and three anacardic acid derivatives (4-6), along with four known anacardic acids (7-10) and two cardanols (11, 12). Their structures were elucidated by 1D and 2D NMR analysis in combination with HRMS experiments. The ability of these compounds to antagonize Bcl-xL/Bak and Mcl-1/Bid association was determined, using a protein-protein interaction assay, but only anacardic acid derivatives (4-10) exhibited significant binding properties, with Ki values ranging from 0.2 to 18 μM. Protein-ligand NMR experiments further revealed that anacardic acid 9, the most active compound, does not interact with the anti-apoptotic proteins Bcl-xL and Mcl-1 but instead interacts with pro-apoptotic protein Bid.
The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of the recycling process Intco Malaysia (EU register number RECYC309), which uses the VACUNITE (EREMA basic and Polymetrix SSP V-leaN) technology. The input consists of hot caustic washed and dried poly(ethylene terephthalate) (PET) flakes mainly originating from collected post-consumer PET containers, with no more than 5% PET from non-food consumer applications. The flakes are pre-decontaminated in the ■■■■■ at ■■■■■ under ■■■■■ (step 2), then extruded and pelletised. The ■■■■■ pellets are then ■■■■■ and submitted to solid-state polycondensation (SSP) at ■■■■■ under ■■■■■ and ■■■■■. Having examined the challenge tests provided, the Panel concluded that the step 2 (flake reactor) and steps 4 and 5 (preheating and SSP) are critical for determining the decontamination efficiency of the process. The operating parameters to control the performance are temperature, pressure and residence time for steps 2, 4 and 5 as well as the ■■■■■ for steps 4 and 5. It was demonstrated that this recycling process is able to ensure that the level of migration of potential unknown contaminants into food is below the conservatively modelled migration of 0.1 μg/kg food. Therefore, the Panel concluded that the recycled PET obtained from this process is not of safety concern, when used at up to 100% for the manufacture of materials and articles for contact with all types of foodstuffs, including drinking water, for long-term storage at room temperature or below, with or without hotfill. The final articles made of this recycled PET are not intended to be used in microwave and conventional ovens and such uses are not covered by this evaluation.
The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of the recycling process INTCO MALAYSIA (EU register number RECYC236), which uses the EREMA Basic technology. The input material is hot caustic washed and dried poly(ethylene terephthalate) (PET) flakes originating from collected post-consumer PET containers, including no more than 5% PET from non-food consumer applications. The flakes are heated in a continuous reactor under vacuum before being extruded. Having examined the challenge test provided, the Panel concluded that the continuous reactor (step 2, for which a challenge test was provided) is critical in determining the decontamination efficiency of the process. The operating parameters to control the performance of this step are temperature, pressure and residence time. It was demonstrated that this recycling process is able to ensure a level of migration of potential unknown contaminants into food below the conservatively modelled migration of 0.1 μg/kg food, derived from the exposure scenario for infants when such recycled PET is used at up to 100%. Therefore, the Panel concluded that the recycled PET obtained from this process is not considered to be of safety concern when used at up to 100% for the manufacture of materials and articles for contact with all types of foodstuffs, including drinking water, for long-term storage at room temperature. Articles made of this recycled PET are not intended to be used in microwave and conventional ovens and such uses are not covered by this evaluation.