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

Résultats de recherche: Contribution à un événement scientifique (non publié)Poster

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Résumé

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).
langue originaleAnglais
PagesBook of Abstracts, ASMC 11, St. Petersburg, Russia, August 21-25, 2011, P157
Nombre de pages1
étatNon publié - 2011
EvénementASMC11 (4th International Symposium on Advances in Synthetic and Medicinal Chemistry). - Saint-Petersbourg, Russie
Durée: 21 août 2011 → …

Une conférence

Une conférenceASMC11 (4th International Symposium on Advances in Synthetic and Medicinal Chemistry).
PaysRussie
La villeSaint-Petersbourg
période21/08/11 → …

Empreinte digitale

Tryptophan Oxygenase
Thiosemicarbazones
Oncology
Methisazone
Bearings (structural)
Indazoles
Ribonucleotides
Chelation
Bioactivity
Tryptophan
Antineoplastic Agents
Modulators
Antiviral Agents
Environmental impact
Metals
Enzymes

Citer ceci

Dolusic, E., Modaffari, S., Larrieu, P., Vancraeynest, C., Pilotte, L., Colau, D., ... 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 présenté � ASMC11 (4th International Symposium on Advances in Synthetic and Medicinal Chemistry)., Saint-Petersbourg, Russie.
Dolusic, Eduard ; Modaffari, Sara ; Larrieu, Pierre ; Vancraeynest, Christelle ; Pilotte, Luc ; Colau, Didier ; Stroobant, Vincent ; Wouters, Johan ; Masereel, Bernard ; Van den Eynde, Benoît ; Frédérick, Raphaël. / Aromatic Thiosemicarazones are inhibitors of tryptophan 2,3-Dioxygenase (TDO), an emerging target for cancer treatment. Poster présenté � ASMC11 (4th International Symposium on Advances in Synthetic and Medicinal Chemistry)., Saint-Petersbourg, Russie.1 p.
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title = "Aromatic Thiosemicarazones are inhibitors of tryptophan 2,3-Dioxygenase (TDO), an emerging target for cancer treatment",
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-T{\'e}l{\'e}vie 7.4.543.07 and by the Walloon Region (grant 'CANTOL' n° 5678).",
author = "Eduard Dolusic and Sara Modaffari and Pierre Larrieu and Christelle Vancraeynest and Luc Pilotte and Didier Colau and Vincent Stroobant and Johan Wouters and Bernard Masereel and {Van den Eynde}, Beno{\^i}t and Rapha{\"e}l Fr{\'e}d{\'e}rick",
year = "2011",
language = "English",
pages = "Book of Abstracts, ASMC 11, St. Petersburg, Russia, August 21--25, 2011, P157",
note = "ASMC11 (4th International Symposium on Advances in Synthetic and Medicinal Chemistry). ; Conference date: 21-08-2011",

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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', ASMC11 (4th International Symposium on Advances in Synthetic and Medicinal Chemistry)., Saint-Petersbourg, Russie, 21/08/11 p. Book of Abstracts, ASMC 11, St. Petersburg, Russia, August 21-25, 2011, P157.

Aromatic Thiosemicarazones are inhibitors of tryptophan 2,3-Dioxygenase (TDO), an emerging target for cancer treatment. / Dolusic, Eduard; Modaffari, Sara; Larrieu, Pierre; Vancraeynest, Christelle; Pilotte, Luc; Colau, Didier; Stroobant, Vincent; Wouters, Johan; Masereel, Bernard; Van den Eynde, Benoît; Frédérick, Raphaël.

2011. Book of Abstracts, ASMC 11, St. Petersburg, Russia, August 21-25, 2011, P157 Poster présenté � ASMC11 (4th International Symposium on Advances in Synthetic and Medicinal Chemistry)., Saint-Petersbourg, Russie.

Résultats de recherche: Contribution à un événement scientifique (non publié)Poster

TY - CONF

T1 - Aromatic Thiosemicarazones are inhibitors of tryptophan 2,3-Dioxygenase (TDO), an emerging target for cancer treatment

AU - Dolusic, Eduard

AU - Modaffari, Sara

AU - Larrieu, Pierre

AU - Vancraeynest, Christelle

AU - Pilotte, Luc

AU - Colau, Didier

AU - Stroobant, Vincent

AU - Wouters, Johan

AU - Masereel, Bernard

AU - Van den Eynde, Benoît

AU - Frédérick, Raphaël

PY - 2011

Y1 - 2011

N2 - 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).

AB - 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).

M3 - Poster

SP - Book of Abstracts, ASMC 11, St. Petersburg, Russia, August 21-25, 2011, P157

ER -

Dolusic E, Modaffari S, Larrieu P, Vancraeynest C, Pilotte L, Colau D et al.. Aromatic Thiosemicarazones are inhibitors of tryptophan 2,3-Dioxygenase (TDO), an emerging target for cancer treatment. 2011. Poster présenté � ASMC11 (4th International Symposium on Advances in Synthetic and Medicinal Chemistry)., Saint-Petersbourg, Russie.