Jacques Royer
Paris Descartes University
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Featured researches published by Jacques Royer.
European Journal of Medicinal Chemistry | 2013
Pascale Coric; Serge Turcaud; Florence Souquet; Laurence Briant; Jacques Royer; Nathalie Chazal; Serge Bouaziz
Bevirimat (2), the first-in-class HIV-1 maturation inhibitor, shows a low efficacy due essentially to the natural polymorphism of its target, the CA-SP1 junction. Moreover, its low hydrosolubility makes it difficult to study its interaction with the CA-SP1 junction. We have synthesized new derivatives of bevirimat by adding different hydrophilic substituents at the C-28 position to improve their hydrosolubility and perform the structural study of a complex by NMR. Synthesis of the new derivatives, the effect of substituents at the C-28 position and their hydrosolubility are discussed. The ability of these molecules to inhibit viral infection and their cytotoxicity is assessed. Compared to the well-known bevirimat (2), one of our compounds (16) shows a higher hydrosolubility associated with a 2.5 fold increase in activity, a higher selectivity index and a better antiviral profile. Moreover, for the first time a direct interaction between a derivative of bevirimat (16) and the domain CA-SP1-NC is shown by NMR. Information from this study should allow us to decipher the mechanism by which bevirimat inhibits HIV-1 maturation and how the natural polymorphism of the spacer peptide SP1 triggers resistance to inhibitors.
Journal of Pharmacology and Experimental Therapeutics | 2009
Thomas Storme; Alain Deroussent; Lionel Mercier; Elise Prost; Micheline Re; Fabienne Munier; Thierry Martens; Philippe Bourget; Gilles Vassal; Jacques Royer; Angelo Paci
Ifosfamide is a well known prodrug for cancer treatment with cytochrome P450 metabolism. It is associated with both antitumor activity and toxicities. Isophosphoramide mustard is the bisalkylating active metabolite, and acrolein is a urotoxic side product. Because acrolein toxicity is limited by coadministration of sodium mercaptoethanesulfonate, the incidence of urotoxicity has been lowered. Current evidence suggests that chloroacetaldehyde, a side-chain oxidation metabolite, is responsible for neurotoxicity and nephrotoxicity. The aim of our research is to prevent chloroacetaldehyde formation using new enantioselectively synthesized ifosfamide analogs, i.e., C7,C9-dimethyl-ifosfamide. We hypothesize that reduced toxicogenic catabolism may induce less toxicity without changing anticancer activity. Metabolite determinations of the dimethyl-ifosfamide analogs were performed using liquid chromatography and tandem mass spectrometry after in vitro biotransformation by drug-induced rat liver microsomes and human microsomes expressing the main CYP3A4 and minor CYP2B6 enzymes. Both human and rat microsomes incubations produced the same N-deschloroalkylated and 4-hydroxylated metabolites. A coculture assay of 9L rat glioblastoma cells and rat microsomes was performed to evaluate their cytotoxicity. Finally, a mechanistic study using 31P NMR kinetics allowed estimating the alkylating activity of the modified mustards. The results showed that C7,C9-dimethyl-ifosfamide exhibited increased activities, although they were still metabolized through the same N-deschloroalkylation pathway. Analogs were 4 to 6 times more cytotoxic than ifosfamide on 9L cells, and the generated dimethylated mustards were 28 times faster alkylating agents than ifosfamide mustards. Among these new ifosfamide analogs, the 7S,9R-enantiomer will be assessed for further in vivo investigations for its anticancer activity and its toxicological profile.
European Journal of Medicinal Chemistry | 2015
Valérie Toum; Julie Bolley; Yoann Lalatonne; Carole Barbey; Laurence Motte; Marc Lecouvey; Jacques Royer; Nathalie Dupont; Joëlle Pérard-Viret
In silico optimisation, synthesis and binding evaluation of αvβ3 integrins affinity for precursors of a new RGD peptidomimetics family are presented. The 2-pyrrolidinone building block was obtained by condensation of l-lysine with dimethoxydihydrofuran followed by reduction. The ring was functionalized with a carboxylic acid and a guanidinium appendage. On the pyrrolidinone heterocycle, the effects on affinity of position, length and relative geometry of the two acid or basic functionalized side chains introduced on the pyrrolidinone ring have been previously evaluated by docking studies. Peptidomimetics have finally been evaluated by competition binding assays for αvβ3 integrins affinity using radio-ligands.
Synlett | 2002
Loic Planas; Joëlle Pérard-Viret; Jacques Royer; Mohamed Selkti; Alain Thomas
Vinylogous Mukaiyama aldol type reaction of chiral non-racemic silyloxypyrroles followed by acidic treatment affords an efficient asymmetric access to 1-azaspiro[4.4]nonanes in high diastereoisomeric excess (un to 79%).
Tetrahedron Letters | 2010
Mounira Benamer; Serge Turcaud; Jacques Royer
European Journal of Organic Chemistry | 2009
Farouk Berhal; Sébastien Tardy; Joëlle Pérard-Viret; Jacques Royer
Tetrahedron Letters | 2010
Joëlle Pérard-Viret; Florence Souquet; Marie-Line Manisse; Jacques Royer
Journal of Chromatography B | 2005
Thomas Storme; Lionel Mercier; Alain Deroussent; Micheline Re; Thierry Martens; Jacques Royer; Philippe Bourget; Gilles Vassal; Angelo Paci
Tetrahedron-asymmetry | 2010
Farouk Berhal; Joëlle Pérard-Viret; Jacques Royer
European Journal of Organic Chemistry | 2009
Carine Vaxelaire; Florence Souquet; Marie-Isabelle Lannou; Janick Ardisson; Jacques Royer