title: Thiosemicarbazide, a fragment with promising indolamine-2,3-dioxygenase (IDO) inhibition properties.
abstract: With the aim to explore the interest of the thiosemicarbazide scaffold for the inhibition of the indoleamine 2,3-dioxygenase (IDO), a promising therapeutic target for anticancer immunotherapy, a series of 32 phenylthiosemicarbazide derivatives was prepared and their IDO inhibition evaluated. Our study demonstrated that among these derivatives, compound 14 characterized with a 4-cyanophenyl group on the thiosemicarbazide was the more potent IDO inhibitor in this series being endowed with an IC50 of 1.2 μM. The SAR depicted showed that substitution in the 3- and 4-position relative to the phenylthiosemicarbazide are very promising whereas substitution in the 2-position always leads to less potent or inactive derivatives. In fact the study highlighted a novel interesting scaffold for IDO inhibition for further development.
authors.affiliation: Namur Medicine & Drug Innovation Center (NAMEDIC-NARILIS), University of Namur (UNamur), 61 rue de Bruxelles, 5000 Namur, Belgium.
authors.forename: Silvia
authors.initials: S
authors.lastname: Serra
authors.affiliation: Namur Medicine & Drug Innovation Center (NAMEDIC-NARILIS), University of Namur (UNamur), 61 rue de Bruxelles, 5000 Namur, Belgium.
authors.forename: Laurence
authors.initials: L
authors.lastname: Moineaux
authors.affiliation: Namur Medicine & Drug Innovation Center (NAMEDIC-NARILIS), University of Namur (UNamur), 61 rue de Bruxelles, 5000 Namur, Belgium.
authors.forename: Christelle
authors.initials: C
authors.lastname: Vancraeynest
authors.affiliation: Namur Medicine & Drug Innovation Center (NAMEDIC-NARILIS), University of Namur (UNamur), 61 rue de Bruxelles, 5000 Namur, Belgium.
authors.forename: Bernard
authors.initials: B
authors.lastname: Masereel
authors.affiliation: Namur Medicine & Drug Innovation Center (NAMEDIC-NARILIS), University of Namur (UNamur), 61 rue de Bruxelles, 5000 Namur, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Wouters
authors.affiliation: Namur Medicine & Drug Innovation Center (NAMEDIC-NARILIS), University of Namur (UNamur), 61 rue de Bruxelles, 5000 Namur, Belgium. Electronic address: lionel.pochet@unamur.be.
authors.forename: Lionel
authors.initials: L
authors.lastname: Pochet
authors.affiliation: Medicinal Chemistry Research Group (CMFA), Louvain Drug Research Institute (LDRI), Université Catholique de Louvain (UCL), 73 Avenue Mounier, B1.73.10, 1200 Bruxelles, Belgium. Electronic address: raphael.frederick@uclouvain.be.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Frédérick
mesh_terms: D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D012663:Semicarbazides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D012663:Semicarbazides; C005151:thiosemicarbazide
keywords: IDO; Immunotherapy; Indoleamine 2,3-dioxygenase; Molecular modelling; Thiosemicarbazide