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

Eduard Dolusic; Pierre Larrieu; Céline Meinguet; Delphine Colette; Arnaud Rives; Sébastien Blanc; Thierry Ferain; Luc Pilotte; Vincent Stroobant; Johan Wouters; Benoît Van den Eynde; Bernard Masereel; Evelyne Delfourne; Raphaël Frédérick

doi:10.1016/j.bmcl.2012.11.036

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

Eduard Dolusic, Pierre Larrieu, Céline Meinguet, Delphine Colette, Arnaud Rives, Sébastien Blanc, Thierry Ferain, Luc Pilotte, Vincent Stroobant, Johan Wouters, Benoît Van den Eynde, Bernard Masereel, Evelyne Delfourne, Raphaël Frédérick

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Abstract

Tsitsikammamines are marine alkaloids whose structure is based on the pyrroloiminoquinone scaffold. These and related compounds have attracted attention due to various interesting biological properties, including cytotoxicity, topoisomerase inhibition, antimicrobial, antifungal and antimalarial activity. Indoleamine 2,3-dioxygenase (IDO1) is a well-established therapeutic target as an important factor in the tumor immune evasion mechanism. In this preliminary communication, we report the inhibitory activity of tsitsikammamine derivatives against IDO1. Tsitsikammamine A analogue 11b displays submicromolar potency in an enzymatic assay. A number of derivatives are also active in a cellular assay while showing little or no activity towards tryptophan 2,3-dioxygenase (TDO), a functionally related enzyme. This IDO1 inhibitory activity is rationalized by molecular modeling studies. An interest is thus established in this class of compounds as a potential source of lead compounds for the development of new pharmaceutically useful IDO1 inhibitors.

Original language	English
Pages (from-to)	47-54
Number of pages	8
Journal	Bioorganic and medicinal chemistry letters
Volume	23
Issue number	1
Early online date	24 Nov 2012
DOIs	https://doi.org/10.1016/j.bmcl.2012.11.036
Publication status	Published - 1 Jan 2013
Event	JFB 2011. - Liege, Belgium Duration: 19 May 2011 → …

Keywords

Cancer immunology
Indoleamine 2,3-dioxygenase
Molecular modeling
Pyrroloiminoquinones
Tsitsikammamines

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10.1016/j.bmcl.2012.11.036

http://www.sciencedirect.com/science/article/pii/S0960894X12014795

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Projects

1 Finished

CANTOL: Design and synthesis of indolamine dioxygenase (IDO) for the treatment of cancer

MASEREEL, B., WOUTERS, J., Dolušić, E., FREDERICK, R., POUYEZ, J., Van den Eynde, B. J., Frère, J., Moser, M., Jean-Marie, B., Combalbert, J. & Stephenne, J.

1/04/08 → 31/03/12

Project: Research

Equipment

Physical Chemistry and characterization(PC2)

Johan Wouters (Manager) & Carmela Aprile (Manager)

Technological Platform Physical Chemistry and characterization

Facility/equipment: Technological Platform

Activities

5 Participation in conference

47th RICT: Drug Discovery and Selection.

Eduard Dolusic (Poster)

6 Jul 2011 → 8 Jul 2011

Activity: Participating in or organising an event types › Participation in conference

JFB 2011.

Eduard Dolusic (Speaker)

19 May 2011 → 20 May 2011

Activity: Participating in or organising an event types › Participation in conference

XVIIIeme JOURNEE JEUNES CHERCHEURS

Eduard Dolusic (Poster)

4 Feb 2011

Activity: Participating in or organising an event types › Participation in conference

Cite this

Dolusic, E., Larrieu, P., Meinguet, C., Colette, D., Rives, A., Blanc, S., Ferain, T., Pilotte, L., Stroobant, V., Wouters, J., Van den Eynde, B., Masereel, B., Delfourne, E., & Frédérick, R. (2013). Indoleamine 2,3-Dioxygenase Inhibitory Activity of Derivatives of Marine Alkaloid Tsitsikammamine A. Bioorganic and medicinal chemistry letters, 23(1), 47-54. https://doi.org/10.1016/j.bmcl.2012.11.036

Dolusic, Eduard ; Larrieu, Pierre ; Meinguet, Céline ; Colette, Delphine ; Rives, Arnaud ; Blanc, Sébastien ; Ferain, Thierry ; Pilotte, Luc ; Stroobant, Vincent ; Wouters, Johan ; Van den Eynde, Benoît ; Masereel, Bernard ; Delfourne, Evelyne ; Frédérick, Raphaël. / Indoleamine 2,3-Dioxygenase Inhibitory Activity of Derivatives of Marine Alkaloid Tsitsikammamine A. In: Bioorganic and medicinal chemistry letters. 2013 ; Vol. 23, No. 1. pp. 47-54.

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abstract = "Tsitsikammamines are marine alkaloids whose structure is based on the pyrroloiminoquinone scaffold. These and related compounds have attracted attention due to various interesting biological properties, including cytotoxicity, topoisomerase inhibition, antimicrobial, antifungal and antimalarial activity. Indoleamine 2,3-dioxygenase (IDO1) is a well-established therapeutic target as an important factor in the tumor immune evasion mechanism. In this preliminary communication, we report the inhibitory activity of tsitsikammamine derivatives against IDO1. Tsitsikammamine A analogue 11b displays submicromolar potency in an enzymatic assay. A number of derivatives are also active in a cellular assay while showing little or no activity towards tryptophan 2,3-dioxygenase (TDO), a functionally related enzyme. This IDO1 inhibitory activity is rationalized by molecular modeling studies. An interest is thus established in this class of compounds as a potential source of lead compounds for the development of new pharmaceutically useful IDO1 inhibitors.",

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Dolusic, E, Larrieu, P, Meinguet, C, Colette, D, Rives, A, Blanc, S, Ferain, T, Pilotte, L, Stroobant, V, Wouters, J, Van den Eynde, B, Masereel, B, Delfourne, E & Frédérick, R 2013, 'Indoleamine 2,3-Dioxygenase Inhibitory Activity of Derivatives of Marine Alkaloid Tsitsikammamine A', Bioorganic and medicinal chemistry letters, vol. 23, no. 1, pp. 47-54. https://doi.org/10.1016/j.bmcl.2012.11.036

Indoleamine 2,3-Dioxygenase Inhibitory Activity of Derivatives of Marine Alkaloid Tsitsikammamine A. / Dolusic, Eduard; Larrieu, Pierre; Meinguet, Céline; Colette, Delphine; Rives, Arnaud; Blanc, Sébastien; Ferain, Thierry; Pilotte, Luc; Stroobant, Vincent; Wouters, Johan; Van den Eynde, Benoît; Masereel, Bernard; Delfourne, Evelyne; Frédérick, Raphaël.

In: Bioorganic and medicinal chemistry letters, Vol. 23, No. 1, 01.01.2013, p. 47-54.

Research output: Contribution to journal › Article

TY - JOUR

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

AU - Dolusic, Eduard

AU - Larrieu, Pierre

AU - Meinguet, Céline

AU - Colette, Delphine

AU - Rives, Arnaud

AU - Blanc, Sébastien

AU - Ferain, Thierry

AU - Pilotte, Luc

AU - Stroobant, Vincent

AU - Wouters, Johan

AU - Van den Eynde, Benoît

AU - Masereel, Bernard

AU - Delfourne, Evelyne

AU - Frédérick, Raphaël

PY - 2013/1/1

Y1 - 2013/1/1

N2 - Tsitsikammamines are marine alkaloids whose structure is based on the pyrroloiminoquinone scaffold. These and related compounds have attracted attention due to various interesting biological properties, including cytotoxicity, topoisomerase inhibition, antimicrobial, antifungal and antimalarial activity. Indoleamine 2,3-dioxygenase (IDO1) is a well-established therapeutic target as an important factor in the tumor immune evasion mechanism. In this preliminary communication, we report the inhibitory activity of tsitsikammamine derivatives against IDO1. Tsitsikammamine A analogue 11b displays submicromolar potency in an enzymatic assay. A number of derivatives are also active in a cellular assay while showing little or no activity towards tryptophan 2,3-dioxygenase (TDO), a functionally related enzyme. This IDO1 inhibitory activity is rationalized by molecular modeling studies. An interest is thus established in this class of compounds as a potential source of lead compounds for the development of new pharmaceutically useful IDO1 inhibitors.

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KW - Cancer immunology

KW - Indoleamine 2,3-dioxygenase

KW - Molecular modeling

KW - Pyrroloiminoquinones

KW - Tsitsikammamines

U2 - 10.1016/j.bmcl.2012.11.036

DO - 10.1016/j.bmcl.2012.11.036

M3 - Article

C2 - 23218716

AN - SCOPUS:84871024705

VL - 23

SP - 47

EP - 54

JO - Bioorganic and medicinal chemistry letters

JF - Bioorganic and medicinal chemistry letters

SN - 0960-894X

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T2 - JFB 2011.

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ER -