Aromatic Thiosemicarazones are inhibitors of tryptophan 2,3-Dioxygenase (TDO), an emerging target for cancer treatment

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

Research output: Contribution to conferencePoster

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Abstract

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 properties2 and to the inhibitory activity on ribonucleotide reductase3 in particular. Compounds of this class, such as marboran and triapine, are already used in medical practice. It has recently been discovered that a hepatic enzyme involved in the tryptophan catabolism, tryptophan 2,3-dioxygenase (TDO), displays antimicrobial and immunoregulatory effects.4 It has also been shown to be a key modulator of neurogenesis and anxiety-related behavior in mice5 as well as a common mediator of genetic and environmental impacts in depression.6 TDO thus represents an emerging target for pharmacological intervention. We have synthesized a series of thiosemicarbazones (1) bearing a(n) (hetero)aromatic moiety, such as phenyl, indole, indazole, naphthalene, imidazole and quinoline, as well as optional substituents on the thiosemicarbazone chain. This class of compounds was evaluated in a cellular test against TDO and showed an inhibitory potency with the best compounds possessing IC50s in the micromolar range. A new pharmacological profile for aromatic thiosemicarbazones is thus demonstrated. This work was supported by FNRS-Télévie 7.4.543.07 and by the Walloon Region (grant 'CANTOL' n° 5678).
Original languageEnglish
PagesBook of Abstracts, ASMC 11, St. Petersburg, Russia, August 21-25, 2011, P157
Number of pages1
Publication statusUnpublished - 2011
EventASMC11 (4th International Symposium on Advances in Synthetic and Medicinal Chemistry). - Saint-Petersbourg, Russian Federation
Duration: 21 Aug 2011 → …

Conference

ConferenceASMC11 (4th International Symposium on Advances in Synthetic and Medicinal Chemistry).
CountryRussian Federation
CitySaint-Petersbourg
Period21/08/11 → …

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    • 4 Participation in conference

    BOSS XIII - 13th Belgian Organic Synthesis Symposium Louvain, 15 - 20 juillet 2012

    Eduard Dolusic (Poster)

    15 Jul 2012

    Activity: Participating in or organising an event typesParticipation in conference

    Annual One-Day Meeting on Medicinal Chemistry of SRC & KVCV (Medchem 2011)

    Eduard Dolusic (Poster)

    25 Nov 2011

    Activity: Participating in or organising an event typesParticipation in conference

    ASMC11 (4th International Symposium on Advances in Synthetic and Medicinal Chemistry).

    Eduard Dolusic (Poster)

    21 Aug 201125 Aug 2011

    Activity: Participating in or organising an event typesParticipation in conference

    Cite this

    Dolusic, E., Modaffari, S., Larrieu, P., Vancraeynest, C., Pilotte, L., Colau, D., Stroobant, V., Wouters, J., Masereel, B., Van den Eynde, B., & Frédérick, R. (2011). Aromatic Thiosemicarazones are inhibitors of tryptophan 2,3-Dioxygenase (TDO), an emerging target for cancer treatment. Book of Abstracts, ASMC 11, St. Petersburg, Russia, August 21-25, 2011, P157. Poster session presented at ASMC11 (4th International Symposium on Advances in Synthetic and Medicinal Chemistry)., Saint-Petersbourg, Russian Federation.