Eduard Dolusic, Sara Modaffari, Pierre Larrieu, Christelle Vancraeynest, Luc Pilotte, Didier Colau, Vincent Stroobant, Benoît Van den Eynde, Johan Wouters, Bernard Masereel, Raphaël Frédérick

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Thiosemicarbazones have received a great deal of attention due to their antineoplastic, antibacterial, antiviral, and antifungal activity.1 Their biological activity has been attributed to metal chelating properties in general2 and to the inhibitory activity on ribonucleotide reductase in particular.3 Compounds of this class, such as marboran and triapine, are already used in medical practice. Indoleamine 2,3-dioxygenase (IDO) is an extrahepatic heme dioxygenase catalysing tryptophan oxidation in the so-called kynurenine pathway of this amino acid catabolism. IDO is involved in tumoral immune resistance: various human tumours express the enzyme constitutively4 and the development and synthesis of IDO inhibitors has been an active area of research in the recent years.5 A structurally unrelated hepatic enzyme catalysing the same reaction, tryptophan 2,3-dioxygenase (TDO), has lately also been linked to cancer immunopathology.6 Our group very recently described a series of ethenyl indole-based TDO inhibitors yielding LM 10, a potent (IC50 = 2 uM in a cellular test), selective, orally bioavailable compound which, furthermore, shows anti-cancer activity in preclinical in vivo models in mice.7 In this work, the synthesis of a small library of aromatic thiosemicarbazones as well as their evaluation and SAR as TDO inhibitors is described. The best compound (ED 135) is roughly equipotent to LM 10 in the cellular test. A new pharmacological profile for aromatic thiosemicarbazones with a potential in an emerging way of cancer treatment is thus demonstrated.
langue originaleAnglais
PagesBook of Abstracts, Annual One-Day Meeting on Medicinal Chemistry of SRC & KVCV (MedChem 2011), Ghent, 25 November 2011, p. 21
Nombre de pages1
Etat de la publicationPublié - 2011
EvénementAnnual One-Day Meeting on Medicinal Chemistry of SRC & KVCV (Medchem 2011) - Gand, Belgique
Durée: 25 nov. 2011 → …

Une conférence

Une conférenceAnnual One-Day Meeting on Medicinal Chemistry of SRC & KVCV (Medchem 2011)
La villeGand
période25/11/11 → …

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