Indoleamine 2,3-Dioxygenase Inhibitory Activity of Derivatives of Marine Alkaloid Tsitsikammamine A

Eduard Dolusic, Pierre Larrieu, Delphine Colette, Sébastien Blanc, Arnaud Rives, Graeme Fraser, Johan Wouters, Robert Kiss, Benoît Van den Eynde, Bernard Masereel, Evelyne Delfourne, Raphaël Frédérick

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Abstract

Tsitsikammamines belonging to the pyrroloiminoquinone class of marine alkaloids were first isolated and characterized in 1996 from a Latrunculiidae sponge collected in the Tsitsikamma Marine Reserve of South Africa.[1] These and related compounds have attracted attention due to various interesting biological properties, including cytotoxicity, topoisomerase inhibition, antimicrobial and antifungal activity.[2] Recently, two novel regioisomeric series of tsitsikammamine A analogues were described.[3] The products were evaluated in an in vitro antiproliferative test against several cancer and normal (fibroblast) cell lines. This work allowed identifying a cytotoxic synthetic intermediate 1 with an unknown mechanism of action. Indoleamine 2,3-dioxygenase (IDO) was identified as an important factor in the tumor immune evasion mechanism. It was demonstrated that many human tumors express IDO in a constitutive manner.[4] Our groups recently published several articles on the development of new series of IDO inhibitors.[5] Here, we would like to report for the first time on an inhibitory activity of tsitsikammamine derivatives against IDO. Tsitsikammamine A analogue 2 displays submicromolar potency in an enzymatic test. A number of derivatives are also moderately active in a cellular test, establishing interest in this class of compounds as a potential source of leads for the development of new pharmaceutically useful IDO inhibitors.
Original languageFrench
Title of host publicationOral Communication, 25èmes Journées Franco-belges de Pharmacochimie, 19-20/05/11, Liège
Subtitle of host publicationDe la conception à la réalisation en pharmacochimie
Pages22-22
Number of pages1
VolumeOC10
Publication statusPublished - 2011
EventJFB 2011. - Liege, Belgium
Duration: 19 May 2011 → …

Conference

ConferenceJFB 2011.
CountryBelgium
CityLiege
Period19/05/11 → …

Cite this

Dolusic, E., Larrieu, P., Colette, D., Blanc, S., Rives, A., Fraser, G., ... Frédérick, R. (2011). Indoleamine 2,3-Dioxygenase Inhibitory Activity of Derivatives of Marine Alkaloid Tsitsikammamine A. In Oral Communication, 25èmes Journées Franco-belges de Pharmacochimie, 19-20/05/11, Liège: De la conception à la réalisation en pharmacochimie (Vol. OC10, pp. 22-22)
Dolusic, Eduard ; Larrieu, Pierre ; Colette, Delphine ; Blanc, Sébastien ; Rives, Arnaud ; Fraser, Graeme ; Wouters, Johan ; Kiss, Robert ; Van den Eynde, Benoît ; Masereel, Bernard ; Delfourne, Evelyne ; Frédérick, Raphaël. / Indoleamine 2,3-Dioxygenase Inhibitory Activity of Derivatives of Marine Alkaloid Tsitsikammamine A. Oral Communication, 25èmes Journées Franco-belges de Pharmacochimie, 19-20/05/11, Liège: De la conception à la réalisation en pharmacochimie. Vol. OC10 2011. pp. 22-22
@inproceedings{22e5225caca34facbeca082fc7c45b4c,
title = "Indoleamine 2,3-Dioxygenase Inhibitory Activity of Derivatives of Marine Alkaloid Tsitsikammamine A",
abstract = "Tsitsikammamines belonging to the pyrroloiminoquinone class of marine alkaloids were first isolated and characterized in 1996 from a Latrunculiidae sponge collected in the Tsitsikamma Marine Reserve of South Africa.[1] These and related compounds have attracted attention due to various interesting biological properties, including cytotoxicity, topoisomerase inhibition, antimicrobial and antifungal activity.[2] Recently, two novel regioisomeric series of tsitsikammamine A analogues were described.[3] The products were evaluated in an in vitro antiproliferative test against several cancer and normal (fibroblast) cell lines. This work allowed identifying a cytotoxic synthetic intermediate 1 with an unknown mechanism of action. Indoleamine 2,3-dioxygenase (IDO) was identified as an important factor in the tumor immune evasion mechanism. It was demonstrated that many human tumors express IDO in a constitutive manner.[4] Our groups recently published several articles on the development of new series of IDO inhibitors.[5] Here, we would like to report for the first time on an inhibitory activity of tsitsikammamine derivatives against IDO. Tsitsikammamine A analogue 2 displays submicromolar potency in an enzymatic test. A number of derivatives are also moderately active in a cellular test, establishing interest in this class of compounds as a potential source of leads for the development of new pharmaceutically useful IDO inhibitors.",
author = "Eduard Dolusic and Pierre Larrieu and Delphine Colette and S{\'e}bastien Blanc and Arnaud Rives and Graeme Fraser and Johan Wouters and Robert Kiss and {Van den Eynde}, Beno{\^i}t and Bernard Masereel and Evelyne Delfourne and Rapha{\"e}l Fr{\'e}d{\'e}rick",
year = "2011",
language = "Fran{\cc}ais",
volume = "OC10",
pages = "22--22",
booktitle = "Oral Communication, 25{\`e}mes Journ{\'e}es Franco-belges de Pharmacochimie, 19-20/05/11, Li{\`e}ge",

}

Dolusic, E, Larrieu, P, Colette, D, Blanc, S, Rives, A, Fraser, G, Wouters, J, Kiss, R, Van den Eynde, B, Masereel, B, Delfourne, E & Frédérick, R 2011, Indoleamine 2,3-Dioxygenase Inhibitory Activity of Derivatives of Marine Alkaloid Tsitsikammamine A. in Oral Communication, 25èmes Journées Franco-belges de Pharmacochimie, 19-20/05/11, Liège: De la conception à la réalisation en pharmacochimie. vol. OC10, pp. 22-22, JFB 2011., Liege, Belgium, 19/05/11.

Indoleamine 2,3-Dioxygenase Inhibitory Activity of Derivatives of Marine Alkaloid Tsitsikammamine A. / Dolusic, Eduard; Larrieu, Pierre; Colette, Delphine; Blanc, Sébastien; Rives, Arnaud; Fraser, Graeme; Wouters, Johan; Kiss, Robert; Van den Eynde, Benoît; Masereel, Bernard; Delfourne, Evelyne; Frédérick, Raphaël.

Oral Communication, 25èmes Journées Franco-belges de Pharmacochimie, 19-20/05/11, Liège: De la conception à la réalisation en pharmacochimie. Vol. OC10 2011. p. 22-22.

Research output: Contribution in Book/Catalog/Report/Conference proceedingConference contribution

TY - GEN

T1 - Indoleamine 2,3-Dioxygenase Inhibitory Activity of Derivatives of Marine Alkaloid Tsitsikammamine A

AU - Dolusic, Eduard

AU - Larrieu, Pierre

AU - Colette, Delphine

AU - Blanc, Sébastien

AU - Rives, Arnaud

AU - Fraser, Graeme

AU - Wouters, Johan

AU - Kiss, Robert

AU - Van den Eynde, Benoît

AU - Masereel, Bernard

AU - Delfourne, Evelyne

AU - Frédérick, Raphaël

PY - 2011

Y1 - 2011

N2 - Tsitsikammamines belonging to the pyrroloiminoquinone class of marine alkaloids were first isolated and characterized in 1996 from a Latrunculiidae sponge collected in the Tsitsikamma Marine Reserve of South Africa.[1] These and related compounds have attracted attention due to various interesting biological properties, including cytotoxicity, topoisomerase inhibition, antimicrobial and antifungal activity.[2] Recently, two novel regioisomeric series of tsitsikammamine A analogues were described.[3] The products were evaluated in an in vitro antiproliferative test against several cancer and normal (fibroblast) cell lines. This work allowed identifying a cytotoxic synthetic intermediate 1 with an unknown mechanism of action. Indoleamine 2,3-dioxygenase (IDO) was identified as an important factor in the tumor immune evasion mechanism. It was demonstrated that many human tumors express IDO in a constitutive manner.[4] Our groups recently published several articles on the development of new series of IDO inhibitors.[5] Here, we would like to report for the first time on an inhibitory activity of tsitsikammamine derivatives against IDO. Tsitsikammamine A analogue 2 displays submicromolar potency in an enzymatic test. A number of derivatives are also moderately active in a cellular test, establishing interest in this class of compounds as a potential source of leads for the development of new pharmaceutically useful IDO inhibitors.

AB - Tsitsikammamines belonging to the pyrroloiminoquinone class of marine alkaloids were first isolated and characterized in 1996 from a Latrunculiidae sponge collected in the Tsitsikamma Marine Reserve of South Africa.[1] These and related compounds have attracted attention due to various interesting biological properties, including cytotoxicity, topoisomerase inhibition, antimicrobial and antifungal activity.[2] Recently, two novel regioisomeric series of tsitsikammamine A analogues were described.[3] The products were evaluated in an in vitro antiproliferative test against several cancer and normal (fibroblast) cell lines. This work allowed identifying a cytotoxic synthetic intermediate 1 with an unknown mechanism of action. Indoleamine 2,3-dioxygenase (IDO) was identified as an important factor in the tumor immune evasion mechanism. It was demonstrated that many human tumors express IDO in a constitutive manner.[4] Our groups recently published several articles on the development of new series of IDO inhibitors.[5] Here, we would like to report for the first time on an inhibitory activity of tsitsikammamine derivatives against IDO. Tsitsikammamine A analogue 2 displays submicromolar potency in an enzymatic test. A number of derivatives are also moderately active in a cellular test, establishing interest in this class of compounds as a potential source of leads for the development of new pharmaceutically useful IDO inhibitors.

M3 - Article dans les actes d'une conférence/un colloque

VL - OC10

SP - 22

EP - 22

BT - Oral Communication, 25èmes Journées Franco-belges de Pharmacochimie, 19-20/05/11, Liège

ER -

Dolusic E, Larrieu P, Colette D, Blanc S, Rives A, Fraser G et al. Indoleamine 2,3-Dioxygenase Inhibitory Activity of Derivatives of Marine Alkaloid Tsitsikammamine A. In Oral Communication, 25èmes Journées Franco-belges de Pharmacochimie, 19-20/05/11, Liège: De la conception à la réalisation en pharmacochimie. Vol. OC10. 2011. p. 22-22