Catalytic Domain; Cell Line; Ethane/chemistry; Humans; Indoleamine-Pyrrole 2,3,-Dioxygenase/antagonists & inhibitors/chemistry; Indoles/chemistry/pharmacology; Models, Molecular; Protein Interaction Domains and Motifs; Structure-Activity Relationship
Abstract :
[en] Indoleamine 2,3-dioxygenase (IDO) is a heme dioxygenase which has been shown to be involved in the pathological immune escape of diseases such as cancer. The synthesis and structure-activity relationships (SAR) of a novel series of IDO inhibitors based on the indol-2-yl ethanone scaffold is described. In vitro and in vivo biological activities have been evaluated, leading to compounds with IC(50) values in the micromolar range in both tests. Introduction of small substituents in the 5- and 6-positions of the indole ring, indole N-methylation and variations of the aromatic side chain are all well tolerated. An iron coordinating group on the linker is a prerequisite for biological activity, thus corroborating the virtual screening results.
Disciplines :
Oncology
Author, co-author :
Dolusic, Eduard; Facultés Universitaires Notre-Dame de la Paix - Namur - FUNDP
Larrieu, Pierre; Université Catholique de Louvain - UCL
Blanc, Sébastien; Euroscreen
Sapunaric, Frédéric ; Université de Liège - ULiège > Centre d'ingénierie des protéines
Norberg, Bernadette; Facultés Universitaires Notre-Dame de la Paix - Namur - FUNDP
Moineaux, Laurence; Facultés Universitaires Notre-Dame de la Paix - Namur - FUNDP
Colette, Delphine; Facultés Universitaires Notre-Dame de la Paix - Namur - FUNDP
Stroobant, Vincent; Université Catholique de Louvain - UCL
Pilotte, Luc; Université Catholique de Louvain - UCL
Colau, Didier; Université Catholique de Louvain - UCL
Ferain, Thierry; Euroscreen
Fraser, Graeme; Euroscreen
Galleni, Moreno ; Université de Liège - ULiège > Centre d'ingénierie des protéines
Frère, Jean-Marie ; Université de Liège - ULiège > Centre d'ingénierie des protéines
Masereel, Bernard; Facultés Universitaires Notre-Dame de la Paix - Namur - FUNDP
Van den Eynde, Benoit; Université Catholique de Louvain - UCL
Wouters, Johan; Facultés Universitaires Notre-Dame de la Paix - Namur - FUNDP
Frederick, Raphael; Facultés Universitaires Notre-Dame de la Paix - Namur - FUNDP
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