Eur. J. Org. Chem. accepted - 24/03/2016    

A platform of synthetic methodologies to prepare regioselectively potent antimalarial polysubstituted 3-benzylmenadione derivatives has been established involving 1) the naphthol route, starting from either a α-tetralone or a propiophenone, or 2) regioselective Diels–Alder reactions.

Chem. Med. Chem. accepted - 08/03/2015    

Revisiting redox: Redox cyclers were quantified at the electrochemical level and modeled using QSPR predictive tools built in house for a series of 3-benzylmenadiones and their corresponding 3-benzoylmenadione redoxactive metabolites. Drug bioactivation by benzylic oxidation was observed to be crucial and is correlated with the multitarget mechanism of action against Plasmodium spp. involving glutathione reductase and ferric species of hemoglobin.

Joan Guillem Mayans Peñarrubia and Enrique Montagud - M2 students - 07/03/2016    

Joan Guillem Mayans Peñarrubia and Enrique Montagud - two new Master2 students in our team

Joan Leandro COTOS-MUNOZ, a new Post-Doc in the team - 07/03/2016    

Leandro COTOS-MUNOZ, a new Post-Doc in our team

Congratulations to Parastoo for her successful PhD Defense - 16/10/2015    

Title:Parastoo has defended her PhD on the 29th of September 2015. The title of her thesis is "Multivalent Systems Based on Viologen Units: Redox Behaviour and Recognition Properties by Cucurbit[n]urils". Many thanks to the Jury members: Dr Olivier Siri (CINAM, Marseille), Pr Francis Vocanson (Université de Saint-Etienne), Pr Josef Hamacek (CBM, Orléans), Dr Zouhair Asfari and Pr Dominique Trébouet (IPHC, STrasbourg). A special thank to Pr Ali Trabolsi (NYUAD, UAE) for this fruitful collaboration

Congratulations to Elena for her successful PhD Defense - 16/10/2015    

Title:Elena has defended her PhD on the 05th of October 2015. The title of her thesis is "Synthèse totale de (aza)naphtoquinones polysubstituées à visée antiparasitaire". Many thanks to the Jury members: Pr Steeve Lanners (Namur University, Blegium), Dr Maurice Medebielle (Université Claude Bernard Lyon), Dr Florence Mahuteau-Betzer (Institut Curie, Paris), Dr Michel Miesch (UMR 7509, STrasbourg).

FEBS J. published - 03/08/2015    

Investigations regarding the chemistry and mechanism of action of 2-methyl-1,4-naphthoquinone derivatives revealed 3-phenoxymethyl menadiones as a novel anti-schistosomal chemical series. These newly synthesized compounds and their difluoromethylmenadione counterparts were found to be potent and specific inhibitors of Schistosoma mansoni thioredoxin-glutathione reductase (SmTGR), which has been identified as a potential target for anti-schistosomal drugs. The compounds were also tested in enzymic assays using both human flavoenzymes, i.e. glutathione reductase (hGR) and selenium-dependent human thioredoxin reductase (hTrxR), to evaluate the specificity of the inhibition. Structure–activity relationships as well as physico- and electro-chemical studies showed a high potential for the 3-phenoxymethyl menadiones to inhibit SmTGR selectively compared to hGR and hTrxR enzymes, in particular those bearing an α-fluorophenol methyl ether moiety, which improves anti-schistosomal action.

Antiox. Red. Signal. published - 09/03/2015    

Early phagocytosis of glucose-6-phosphate dehydrogenase-deficient erythrocytes parasitized by Plasmodium falciparum were shown to protect G6PD deficient-populations from severe malaria. Here, we investigated the mechanism of a novel antimalarial series, namely 3-substituted-benzyl-menadiones, to understand if these NADPH-consuming redox-cyclers, which induce oxidative stress, mimic the natural protection of G6PD deficiency. We demonstrated that the key benzoylmenadione metabolite of the lead compound acts as an efficient redox-cycler in NADPH-dependent methaemoglobin reduction leading to the continuous formation of reactive oxygen species, ferrylhaemoglobin, and subsequent haemichrome precipitation.

Eur. J. Org. Chem. published - 06/02/2015    

Two efficient phase-transfer-catalyzed protocols for the diastereoselective synthesis of cis and trans isomers of 2,6-diaryltetrahydrothiopyran-4-ones (2,6-DATHTPs) have been developed. In a study of the scope of the reactions, differently substituted 2,6-DATHTPs were successfully accessed in high yields and diastereomeric excesses on both experimental and preparative scales.

Welcome to Aurelia Geyer and Malika OUDRHIRI-SAFIANI - M2 students - 02/02/2015    

Aurelia Geyer and Malika OUDRHIRI-SAFIANI - two new Master2 students in our team

Welcome to Angeline Cherbonnel, a new PhD student - 02/02/2015    

Angeline Cherbonnel is starting a PhD work in collaboartion with Clariant. She will focus her research efforts on unraveling the mechanism of action of metallic oxygen barriers applied in polymers for food and drinks preservation

Congratulations to Xavier Martin-Benlloch who brightly defended his PhD on the 08th of January 2015 - 08/01/2015    

Xavier has defended his PhD on the 08th of January 2015. The title of his thesis is "Synthesis and physicochemical study of a new antiviral flavonoid. Many thanks to the Jury members: Pr Stéphane Quideau (ISM Bordeaux), Pr Ali Trabolsi (NYUAD, UAE), Dr Florence Mahuteau-Betzer (Institut Curie, Paris) and Pr Anne-Lise Lobstein (Laboratoire d'Innovation Thérapeutique, Strasbourg)

Chem. Eur. J. published - 05/01/2015    

In the context of the investigation of drug-induced oxidative stress in parasitic cells, electrochemical properties of a focused library of polysubstituted menadione derivatives were studied by cyclic voltammetry. These values were used, together with compatible measurements from literature (quinones and related compounds), to build and evaluate a predictive structure–redox potential model (quantitative structure–property relationship, QSPR). Able to provide an online evaluation (through Web interface) of the oxidant character of quinones, the model is aimed to help chemists targeting their synthetic efforts towards analogues of desired redox properties. This work has been done in close collaboration between the LCBM (E. Davioud-Charvet and M. Elhabiri) and the group of Chemoinformatics (A. Varnek and D. Horvath). The authors wish to thank the International Center for Frontier Research in Chemistry (ic-FRC) in Strasbourg (ic-FRC-LabEx Chimie des systemes complexes, project entitled “Understanding the mechanisms of antimalarial redox-active substrates in Plasmodium-infected red blood cells: a combined physicochemical and computational approach to unveiling biological complexity”) for creating a proper framework for this scientific collaboration