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

Cite this

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 session presented at ASMC11 (4th International Symposium on Advances in Synthetic and Medicinal Chemistry)., Saint-Petersbourg, Russian Federation.
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 session presented at ASMC11 (4th International Symposium on Advances in Synthetic and Medicinal Chemistry)., Saint-Petersbourg, Russian Federation.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, Russian Federation, 21/08/11 pp. 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 session presented at ASMC11 (4th International Symposium on Advances in Synthetic and Medicinal Chemistry)., Saint-Petersbourg, Russian Federation.

Research output: Contribution to conferencePoster

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 session presented at ASMC11 (4th International Symposium on Advances in Synthetic and Medicinal Chemistry)., Saint-Petersbourg, Russian Federation.