Search

Further advances in understanding the mechanism of action of resveratrol and its application require new analogs to identify the structural determinants for the cell proliferation inhibition potency. Therefore, we synthesized new trans-resveratrol derivatives by using the Wittig and Heck methods, thus modifying the hydroxylation and methoxylation patterns of the parent molecule. Moreover, we also synthesized new ferrocenylstilbene analogs by using an original protective group in the Wittig procedure. By performing cell proliferation assays we observed that the resveratrol derivatives show inhibition on the human colorectal tumor SW480 cell line. On the other hand, cell viability/cytotoxicity assays showed a weaker effects on the human hepatoblastoma HepG2 cell line. Importantly, the lack of effect on non-tumor cells (IEC18 intestinal epithelium cells) demonstrates the selectivity of these molecules for cancer cells. Here, we show that the numbers and positions of hydroxy and methoxy groups are crucial for the inhibition efficacy. In addition, the presence of at least one phenolic group is essential for the antitumoral activity. Moreover, in the series of ferrocenylstilbene analogs, the presence of a hidden phenolic function allows for a better solubilization in the cellular environment and significantly increases the antitumoral activity.

International audience; 2,3-Dihydrobenzofurans are proposed as privileged structures and used as chemical platform to design small compound libraries. By combining molecular docking calculations and experimental verification of biochemical interference, we selected some potential inhibitors of microsomal prostaglandin E2 synthase (mPGES)-1. Starting from low affinity natural product 1, by our combined approach we identified the compounds 19 and 20 with biological activity in the low micromolar range. Our data suggest that the 2,3-dihydrobenzofuran derivatives might be suitable bioinspired lead compounds for development of new generation mPGES-1 inhibitors with increased affinity.

Seven resveratrol-related monomeric stilbenoids were submitted to biomimetic oxidative coupling in the presence of laccase from Trametes versicolor (TvL), and gave racemic dihydrobenzofuran dehydrodimers (±)-15 to (±)-21. These products, after spectral characterization, were submitted to an antiproliferative activity bioassay against SW480 human colon cancer cells. Five racemates were found to be active, and were resolved by chiral HPLC. The pure enantiomers were subjected to circular dichroism measurements to establish their absolute configurations at C-7 and C-8. These enantiomerically pure compounds were submitted to the antiproliferative activity assay towards SW480 cells, and were all shown to be active with IC50 values in the approximate range 20–90 μM. In some cases, a significant difference between the activity of the 7R,8R and 7S,8S enantiomers was observed, but a defined configuration of the stereogenic centers does not appear to be a structural requirement for the activity. The comparison between the most active compounds and the inactive ones strongly suggests that the presence of a methoxy group in the position ortho to the C-4 hydroxy group is highly detrimental to the activity.

Improved protocols for Wittig reaction and palladium-catalyzed Heck coupling give expedient access to a series of unprecedented polyfunctionalized artificial-resveratrol derivatives. In the modified Wittig protocol, trimethylsilyl was used as a highly valuable protective group of the phenolic functions of starting aromatic materials. A clean O-alkylation of hydroxylated stilbenes with ethylene carbonate was also conducted. Thus, Wittig reaction followed by hydroxyethylation take place one-pot with only carbon dioxide as waste. Additionally, a palladium-catalyzed Heck coupling strategy was developed by using ferrocenyl phosphane ligands, and multi-functionalized hydroxylated stilbenes were obtained without the need of any protection/deprotection sequence. Up to six functional groups are introduced by these procedures, which limit the number of reactions steps, the waste toxicity, and the use of costly reagents.

International audience; Industry servitisation, i.e. the manufacturing industry transition towards the integration of services, provides for strong opportunities of new business model development and implementation. However, managing the industrial transformation to such business models means decision-makers are confronted with high decisional complexity. Such dramatic changes affect most enterprise performance drivers, and the interactions of the multiple business and industrial factors influencing the overall company performance make it very difficult for managers to specify consistent and efficient industrial configurations for their business processes. This context explains a concrete need for developing servitisation-dedicated decision support systems (DSS). The objective of the decision aid developed in this paper is to provide operational support which integrates the specific business and industrial features of so-called ‘product–service systems’ in order to study the interactions of different types of performance factors, notably market-oriented versus industrial-oriented factors. These developments are applied to a French Small and Medium Enterprise (SME). The key added values of the paper are (1) to specify a modelling and simulation approach associated to a generic simulator adaptable to various industrial contexts, then (2) to illustrate the concrete decision support provided in a case study of an SME in the business of remanufacturing electrical equipment. The case study highlights capacity management issues in a servitisation context.

SPE IPM UB CT1; International audience; Inducing resistance in plants by the application of elicitors of defense reactions is an attractive plant protection strategy, particularly for grapevine (Vitis vinifera), which is susceptible to severe fungal diseases. Although induced resistance (IR) can be successful under controlled conditions, in most cases, IR is not sufficiently effective for practical disease control under outdoor conditions. Progress in the application of IR requires a better understanding of grapevine defense mechanisms and the ability to monitor defense markers to identify factors, such as physiological and environmental factors, that can impact IR in the vineyard. Volatile organic compounds (VOCs) are well-known plant defense compounds that have received little or no attention to date in the case of grape-pathogen interactions. This prompted us to investigate whether an elicitor, the sulfated laminarin (PS3), actually induces the production of VOCs in grapevine. An online analysis (proton-transfer-reaction quadrupole mass spectrometry) of VOC emissions in dynamic cuvettes and passive sampling in gas-tight bags with solid-phase microextraction-GC-MS under greenhouse conditions showed that PS3 elicited the emission of VOCs. Some of them, such as (E,E)-α-farnesene, may be good candidates as biomarkers of elicitor-IR, whereas methyl salicylate appears to be a biomarker of downy mildew infection. A negative correlation between VOC emission and disease severity suggests a positive role of VOCs in grape defense against diseases.

Part VI: Services, Supply Chains and Operations; International audience; The research presented in this paper is oriented on the transition of the manufacturing industry towards the delivery of product-service system. The paper presents the first results in the development of a decision support system dedicated to help in configuring service-oriented production systems, notably with an objective of capacity management. An illustrative case study is presented, linked to the production of washing machines.

International audience; The transition of manufacturing companies towards Product Service System (PSS) offers was mainly treated in the literature at the strategic level. This paper aims at studying the impact of the transition in operation management, with a specific focus on capacity management. With this purpose we present below a PSS Production System, used as a decision support tool. We first explain conceptually the modelling approach used, and the general concepts. Then we explain how discrete events simulation was applied to study different scenarios and strategy of capacity management on a case study. First results of this feasibility study are discussed.

In the modified Wittig reaction, Tms is used as a highly valuable protecting group of the phenolic functions of the starting arenes.